Tumor nanoparticles based on CXCR1 targeting peptide and Prussian blue and preparation method and application thereof

Abstract

The present invention discloses a tumor nanoparticle based on CXCR1 targeting polypeptide and Prussian blue, wherein the tumor nanoparticle comprises a hollow mesoporous Prussian blue nanoparticle; the surface of the hollow mesoporous Prussian blue nanoparticle is modified with a CXCR1 targeting polypeptide, and a fluorescent dye is loaded inside. The present invention grafts the CXCR1 targeting polypeptide into the hollow mesoporous Prussian blue nanoparticle (PBNPs), organically combines the targeting of CXCR1 with the photothermal effect of Prussian blue, and has a strong killing effect on highly metastatic osteosarcoma cells. This is crucial to the development of a method for effectively controlling the recurrence and metastasis of osteosarcoma, reducing the systemic adverse reactions caused by chemotherapeutic drugs, etc., making the present invention have important theoretical and application value.

Description

Technical Field

[0001] The present invention relates to the technical field of nanoparticles, and in particular to a tumor nanoparticle based on CXCR1 targeting polypeptide and Prussian blue, and a preparation method and application thereof. Background Art

[0002] Osteosarcoma (OS) is one of the most common primary malignant tumors in the musculoskeletal system. The emergence of drug resistance is the main reason for the failure of limb-sparing surgery and metastasis in osteosarcoma patients, and metastasis is the main cause of death in osteosarcoma patients. It is urgent to take active and effective prevention and treatment measures to curb the development of osteosarcoma, so as to maximize the quality of life of patients.

[0003] In tumor research, most of the gene inhibition of CXCR1 is achieved by gene silencing tumor cells through genetic engineering-related technologies, which is far from clinical application. Secondly, Reparixin is a non-competitive allosteric inhibitor of CXCR1 / 2, which acts on a wide range of somatic cells in the human body and has immeasurable toxic side effects when used in vivo. There are two main reasons for the above problems. One is that it is difficult to achieve clinical transformation from existing basic research, which may require the use of multidisciplinary cross-integration. Secondly, general inhibitors are not cell-specific and often have significant toxic side effects on the body while achieving therapeutic effects.

[0004] In previous studies, we first isolated and cultured the highly metastatic Saos2-lung osteosarcoma cell subtype from the lung metastases of osteosarcoma in nude mice. Further studies found that CXCR1 gene inhibition can enhance the chemosensitivity of osteosarcoma to cisplatin and inhibit the metastasis of osteosarcoma. Based on the above results, a targeting peptide that can target CXCR1 was designed (patent has been applied for, patent document CN110343163A), which provides a basis for molecular targeted therapy of osteosarcoma. Based on this peptide, we loaded the chemotherapy drug cisplatin and CXCR1 targeting peptide with silica@ferric oxide nanoparticles to synthesize a nanoparticle with targeted effect, Cis@MFPPC (Advanced Functional Materials, 2019, 29(34): 1902246). However, although the above nanoparticles can achieve the effect of inhibiting osteosarcoma, they will eventually cause the accumulation of chemotherapy drugs in the body, causing certain toxic side effects. Summary of the invention

[0005] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a tumor nanoparticle based on CXCR1 targeting polypeptide and Prussian blue, and a preparation method and application thereof, wherein the tumor nanoparticle is a safer and more efficient osteosarcoma targeted therapeutic preparation.

[0006] The objective of the present invention is achieved through the following technical solutions:

[0007] In a first aspect, the present invention provides a tumor nanoparticle based on CXCR1 targeting polypeptide and Prussian blue, wherein the tumor nanoparticle comprises a hollow mesoporous Prussian blue nanoparticle; the surface of the hollow mesoporous Prussian blue nanoparticle is modified with a CXCR1 targeting polypeptide and a fluorescent dye is loaded inside.

[0008] As a preferred embodiment, the amino acid sequence of the CXCR1 targeting polypeptide is:

[0009] SAKELRCQCIKTYSKPFHPK.

[0010] As a preferred embodiment, the fluorescent dye is Cy7 red fluorescent dye.

[0011] In a second aspect, the present invention provides a method for preparing tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue, comprising the following steps:

[0012] S1. Synthesis of mesoporous Prussian blue nanoparticles: polyvinyl pyrrolidone (PVP), Prussian blue powder and HCl solution are mixed, the obtained transparent solution is heat-treated, and the treated product is centrifuged and washed to obtain mesoporous Prussian blue nanoparticles (MPB);

[0013] S2. Synthesis of hollow mesoporous Prussian blue nanoparticles: polyvinyl pyrrolidone (PVP) is added to a PBS solution containing mesoporous Prussian blue nanoparticles (MPB), and after magnetic stirring, the resulting solution is heat-treated under sterile conditions, and the treated product is centrifuged and washed to obtain hollow mesoporous Prussian blue nanoparticles (PBNPs);

[0014] S3. Synthesis of fluorescently labeled hollow mesoporous Prussian blue nanoparticles: hollow mesoporous Prussian blue nanoparticles are dissolved in PBS solution, fluorescent dye is added to the resulting solution, stirred evenly, centrifuged, washed, and freeze-dried to obtain fluorescently labeled hollow mesoporous Prussian blue nanoparticles (Cy7-PBNPs);

[0015] S4. Synthesis of tumor nanoparticles based on CXCR1 targeting peptide and Prussian blue: amino groups are modified on the surface of fluorescently labeled hollow mesoporous Prussian blue nanoparticles (Cy7-PBNPs), and the CXCR1 targeting peptide is carboxylated. The obtained amino-modified nanoparticles are combined with the carboxylated CXCR1 targeting peptide, and freeze-dried to obtain tumor nanoparticles based on CXCR1 targeting peptide and Prussian blue.

[0016] As a preferred embodiment, in step S1, the heat treatment condition is: treatment at 80° C. for 24 hours.

[0017] As a preferred embodiment, in step S2, the conditions for the heat treatment under sterile conditions are: treatment at 140° C. for 4 hours.

[0018] In a third aspect, the present invention provides a use of the aforementioned tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue in the preparation of a drug for inhibiting CXCR1 activity.

[0019] In a fourth aspect, the present invention provides a use of the aforementioned tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue in the preparation of a drug for treating osteosarcoma.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1) The present invention combines CXCR1 targeting polypeptide and Prussian blue, which not only achieves the targeting effect, but also takes advantage of the photothermal effect of Prussian blue, and greatly improves the therapeutic effect of osteosarcoma through the synergistic effect of the two. And compared with the Cis@MFPPC nanoparticles synthesized in our previous study, it has a better therapeutic effect on osteosarcoma.

[0022] 2) The tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue synthesized in the present invention are crucial to the development of effective methods for controlling the recurrence and metastasis of osteosarcoma, locating the location of tumors, improving the therapeutic effect of osteosarcoma, and reducing the systemic adverse reactions caused by chemotherapeutic drugs. The expected results have important theoretical and application values. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0024] Figure 1 This is the synthesis process of CXCR1@PBNPs nano-targeted particles in Example 1;

[0025] Figure 2 This is a transmission electron microscopy image of the CXCR1@PBNPs nano-targeted particles synthesized in Example 1;

[0026] Figure 3 The results of the cytotoxicity and anti-osteosarcoma effects of the CXCR1@PBNPs nano-targeted particles in vitro in Example 2; Figure 3 A is L929 cells; Figure 3 B is Saos2-lung osteosarcoma cells; *** indicates P < 0.001, ** indicates P < 0.01, * indicates P < 0.05, all data are expressed as mean ± standard deviation, and are derived from three independent experiments, N = 6;

[0027] Figure 4 Statistical analysis results of apoptosis verified by the effect of CXCR1@PBNPs nano-targeted particles in promoting apoptosis of osteosarcoma cells in Example 3, including the photothermal effects of the Cis group, PBNPs+NIR808 group and CXCR1@PBNPs+NIR808 group; *** indicates P<0.001, all data results are expressed as mean ± standard deviation, N=3. DETAILED DESCRIPTION

[0028] The present invention is described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several variations and improvements may be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0029] Our previous studies have shown that genetic inhibition of CXCR1 can enhance the chemotherapy sensitivity of osteosarcoma cells to cisplatin. However, how to achieve precise treatment by targeting CXCR1 in osteosarcoma still needs further in-depth research.

[0030] In a specific embodiment of the present invention, we first utilized the CXCR1 targeting polypeptide (amino acid sequence: SAKELRCQCIKTYSKPFHPK, see the record in patent document CN110343163A for details) synthesized in our early stage. Since it can competitively bind to CXCR1 with IL-8 and can also inhibit the malignant biological characteristics of osteosarcoma, in the present invention, we grafted the CXCR1 targeting polypeptide into hollow mesoporous Prussian blue nanoparticles (PBNPs).

[0031] Prussian blue (PB), also known as ferric ferrocyanide, has a chemical formula of Fe4[Fe(CN)6]3 and is a clinical drug approved by the U.S. Food and Drug Administration (FDA). Prussian blue nanoparticles (PBNPs) play an important role in photoacoustic imaging (PAI), magnetic resonance imaging (MRI), drug delivery, molecular imaging, gene therapy, and photothermal therapy of tumors due to their controllable size and structure and their easy modification. Therefore, we intend to inhibit the proliferation and metastasis of osteosarcoma cells through CXCR1 targeting peptides, enhance the photothermal effect of PBNPs, and thus improve the therapeutic effect of osteosarcoma.

[0032] Through experimental research, we found that we organically combined CXCR1 targeting and Prussian blue photothermal effect, which has a better therapeutic effect on osteosarcoma than the Cis@MFPPC nanoparticles synthesized in our early stage. This is crucial for developing effective methods to control the recurrence and metastasis of osteosarcoma, locate the tumor location, improve the therapeutic effect of osteosarcoma, and reduce the systemic adverse reactions caused by chemotherapy drugs. The expected results have important theoretical and application value.

[0033] In a specific embodiment of the present invention, the method for preparing tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue comprises the following steps:

[0034] S1. Synthesis of mesoporous Prussian blue nanoparticles: polyvinyl pyrrolidone (PVP), Prussian blue powder and HCl solution are mixed, the obtained transparent solution is heat-treated, and the treated product is centrifuged and washed to obtain mesoporous Prussian blue nanoparticles (MPB);

[0035] S2. Synthesis of hollow mesoporous Prussian blue nanoparticles: polyvinyl pyrrolidone (PVP) is added to a PBS solution containing mesoporous Prussian blue nanoparticles (MPB), and after magnetic stirring, the resulting solution is heat-treated under sterile conditions, and the treated product is centrifuged and washed to obtain hollow mesoporous Prussian blue nanoparticles (PBNPs);

[0036] S3. Synthesis of fluorescently labeled hollow mesoporous Prussian blue nanoparticles: hollow mesoporous Prussian blue nanoparticles are dissolved in PBS solution, fluorescent dye is added to the resulting solution, stirred evenly, centrifuged, washed, and freeze-dried to obtain fluorescently labeled hollow mesoporous Prussian blue nanoparticles (Cy7-PBNPs);

[0037] S4. Synthesis of tumor nanoparticles based on CXCR1 targeting peptide and Prussian blue: amino groups are modified on the surface of fluorescently labeled hollow mesoporous Prussian blue nanoparticles (Cy7-PBNPs), and the CXCR1 targeting peptide is carboxylated. The obtained amino-modified nanoparticles are combined with the carboxylated CXCR1 targeting peptide, and freeze-dried to obtain tumor nanoparticles based on CXCR1 targeting peptide and Prussian blue.

[0038] Example

[0039] The following will be combined with the embodiments of the present application to clearly and completely describe the technical solution of the present application. Unless otherwise specified, the reagents and raw materials used can be purchased through commercial channels. The experimental methods in the following examples that do not specify specific conditions are selected according to conventional methods and conditions, or according to the product specifications.

[0040] Example 1

[0041] This embodiment provides a method for synthesizing tumor nanoparticles (CXCR1@PBNPs nano-targeting particles) based on CXCR1 targeting polypeptide and Prussian blue, and the specific steps are as follows:

[0042] (1) Synthesis of mesoporous Prussian blue nanoparticles (MPB): 3.0 g of polyvinyl pyrrolidone (PVP), 132 mg of K3[Fe(CN)6] and HCl solution (0.01 M, 40 ml) were mixed under magnetic stirring. After obtaining a transparent solution, it was placed in an electric oven at 80°C for 24 hours. After repeated centrifugation and washing twice in distilled water, mesoporous Prussian blue nanoparticles (MPB) were obtained. (2) Synthesis of hollow mesoporous Prussian blue nanoparticles (Cy7-PBNPs) labeled with red fluorescence: MPB was dissolved in PBS to prepare a solution with a concentration of 1 mg / ml; 20 ml of PVP (5 mg / ml) was added to 20 ml of the solution containing MPB (1 mg / ml), and then magnetic stirring was performed in a Teflon container for 3 hours. The resulting solution was placed in a stainless steel autoclave and heated in an electric oven at 140°C for 4 hours. After the obtained product was centrifuged, the precipitate was washed twice with distilled water to obtain product 1. 0.3 mg of Cy7 dye was placed in 20 ml of PBS solution containing product 1 (concentration of 1 mg / ml) and magnetically stirred for 3 hours. After centrifugation, the precipitate was washed twice with distilled water to obtain product 2. The obtained product 2 was freeze-dried to obtain hollow mesoporous Prussian blue nanoparticles (Cy7-PBNPs) labeled with Cy7 red fluorescence. (3) Synthesis of CXCR1@PBNPs nano-targeted particles:

[0043] a. Aminated Cy7-PBNPs nanoparticles

[0044] Amino-modified Cy7-PBNPs nanoparticles were prepared by copolymerization. 100 mg of Cy7-PBNPs nanoparticles were dispersed in 10 mL of ultrapure water and 0.4 ml of diethylenetriaminepropyltrimethoxysilane (AEPTMS) was added. The reaction was stirred at 40 ° C for 24 hours and then the product was collected by centrifugation. The reaction product was washed with water and acidic ethanol (repeatedly centrifuged to wash the unreacted AEPTMS) and freeze-dried to obtain amino-modified Cy7-PBNPs nanoparticles.

[0045] b. Carboxyl-modified CXCR1 targeting peptides

[0046] The CXCR1 targeting peptide (SAKELRCQCIKTYSKPFHPK) was conjugated to the carboxyl-PEG-amino group using the 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) activation method. In the presence of EDC, the amino group in the carboxyl-PEG-amino group was grafted with the carboxyl group of glutamic acid in the CXCR1 targeting peptide. The CXCR1 targeting peptide (2 mg / mL, dissolved in deionized water) was added to EDC (pH 5.6, 5 mg / mL) and pre-activated at 37°C for 2 h. The activated CXCR1 targeting peptide was added to the carboxyl-PEG-amino solution (2 mg / mL) dissolved in PBS, and the ratio of the two was 1:1. N-hydroxysuccinimide (NHS, 5 mg / mL) was then added, and the resulting mixture was stirred at room temperature for 24 h. Finally, the amino group in the carboxyl-PEG-amino group was grafted with the carboxyl group of glutamic acid in the CXCR1 targeting peptide to obtain a carboxylated CXCR1 targeting peptide.

[0047] c. Amino-modified Cy7-PBNPs nanoparticles combined with carboxyl-modified CXCR1 targeting peptide

[0048] Finally, the carboxyl group in the carboxyl-modified CXCR1 targeting peptide is combined with the carboxyl group in the amino-modified Cy7-PBNPs nanoparticles. The reaction steps are the same as b, that is, the carboxyl-modified CXCR1 targeting peptide is added to the amino-modified Cy7-PBNPs nanoparticles (2 mg / mL) dissolved in PBS, and the ratio of the two is 1:1. Then N-hydroxysuccinimide (NHS, 5 mg / mL) is added, and the resulting mixture is stirred at room temperature for 24 hours. The resulting product is freeze-dried in a freeze dryer and stored at 4°C for later use. Finally, CXCR1@PBNPs nano-targeted particles are obtained. For details of the synthesis process, see Figure 1 .

[0049] (4) Transmission electron microscopy scanning of CXCR1@PBNPs nano-targeted particles: Transmission electron microscopy (TEM) photos were obtained using a JEM-2100F high-resolution transmission electron microscope from JEOL, Japan, with an operating voltage of 200 kV. Before testing, the CXCR1@PBNPs nano-targeted particle sample prepared in step (3) was ground into powder and ultrasonically dispersed in ethanol for 10 minutes to obtain a CXCR1@PBNPs nano-particle dispersion. The TEM sample was prepared by dropping 1 drop of CXCR1@PBNPs nano-particle dispersion with a concentration of 1 mg / mL onto a 230-mesh copper grid and drying at room temperature. Three fields of view at different positions were randomly selected during scanning. Through the scanning electron microscope, we can see that the nanoparticles have good dispersion and uniform particle size. See the specific results for details. Figure 2 .

[0050] Example 2

[0051] This example investigates the cytotoxicity and inhibitory effect of CXCR1@PBNPs nano-targeted particles on osteosarcoma cells, and specifically uses the CCK-8 method to detect the effect of CXCR1@PBNPs nano-targeted particles on the proliferation of Saos2-lung osteosarcoma cells and L929 cells. The specific steps are as follows:

[0052] (1) Cell preparation

[0053] Take L929 cells (purchased from the cell bank of the Chinese Academy of Sciences) and Saos2-lung osteosarcoma cells (made by our research group, refer to Du, L., Fan, Q., Tu, B., et al. Establishment and characterization of a new highly metastatic human osteosarcoma cell line derived from Saos2. Int J Clin Exp Pathol, 2014, 7 (6): 2871-82) in logarithmic phase growth, digest them with trypsin, and centrifuge them at 300g for 5 minutes. After centrifugation, remove the supernatant, resuspend the cells in complete medium, and count them separately. Inoculate 5000 cells / well into a 96-well plate.

[0054] (2) Cytotoxicity test

[0055] After the cells adhered to the wall, solutions containing different concentrations of CXCR1@PBNPs nanoparticles were added to the 96-well plate containing L929 cells, with 6 replicate wells for each concentration. The solutions containing different concentrations of CXCR1@PBNPs nanoparticles were obtained by dissolving the CXCR1@PBNPs nanoparticles synthesized in Example 1 in the cell culture medium.

[0056] The cells added with solutions containing different concentrations of CXCR1@PBNPs nanoparticles were measured for absorbance using the CCK-8 method to detect cell viability. First, the CCK-8 solution was prepared with DMEM complete medium at a ratio of 1:10, and the culture medium in the cells was replaced with the newly prepared CCK-8 solution, 110μl / well. Incubate in an incubator for 2.5h. After 2.5h, the cells added with CCK-8 were taken out, the bubbles in the wells were removed, and the absorbance value at 450nm was measured in an ELISA reader.

[0057] The results are as follows Figure 3As shown in A, CXCR1@PBNPs nanoparticles have a slight inhibitory effect on L929 cell proliferation at a concentration of 400μg / ml, but it is not statistically significant, and this concentration is already a relatively high concentration. Therefore, CXCR1@PBNPs nanoparticles have no obvious cytotoxicity to L929 cells within the concentration we tested. At the same time, 200μg / ml was determined as the experimental concentration of nanoparticles, and we further used Saos2-lung osteosarcoma cells to verify its anti-tumor effect.

[0058] (3) Anti-tumor effect test

[0059] Cisplatin (Cis) 10 μg / ml and Cis@MFPPC nanoparticles 10 μg / ml were used as positive control groups, PBNPs nanoparticles 200 μg / ml + NIR 808nm (5 min) were used as control groups, and CXCR1@PBNPs nanoparticles 200 μg / ml + NIR 808nm (5 min) were used as experimental groups. After stimulating the Saos2-lung osteosarcoma cells obtained in step (1), the absorbance was measured by the CCK-8 method to detect cell viability. Saos2-lung osteosarcoma cells without any nanoparticles were used as blank control group (Con). The specific steps for measuring absorbance are as follows: first, CCK-8 solution was prepared with DMEM complete culture medium at a ratio of 1:10, and the culture medium in the cells was replaced with the newly prepared CCK-8 solution, 110 μl / well. Incubate in an incubator for 2.5 hours. After 2.5 hours, the cells to which CCK-8 was added were taken out, the bubbles in the wells were removed, and the cells were placed in an ELISA reader to measure the absorbance at 450 nm.

[0060] The Cis@MFPPC nanoparticles are prepared by the method described in patent document CN110343163A, and the PBNPs nanoparticles are nanoparticles that are not loaded with CXCR1 targeting polypeptides.

[0061] The results are as follows Figure 3 As shown in B, the same 5-minute treatment of osteosarcoma cells showed a significant difference compared to cisplatin ( Figure 3 Cis group shown in B), Cis@MFPPC nanoparticles ( Figure 3 Cis@MFPPC group (B) and PBNPs nanoparticles + NIR 808nm light ( Figure 3 Cis@MFPPC+NIR808 group (B), CXCR1@PBNPs nanoparticles 200 μg / ml+NIR808 nm ( Figure 3 The CXCR1@PBNPs+NIR808 group shown in B) had the best anti-osteosarcoma cell proliferation effect.

[0062] Example 3

[0063] This example investigates the effect of CXCR1@PBNPs nano-targeted particles on promoting apoptosis of osteosarcoma cells, and the specific steps are as follows:

[0064] (1) Cell inoculation and culture

[0065] Saos2-lung osteosarcoma cells were digested, counted and prepared into cell suspension, and 5×10 5 Cells were inoculated in a six-well plate at a volume of 10 cells / well of a 6-well plate. After the cells adhered to the wall, 10 μg / ml of cisplatin (Cis) was added as a positive control, 200 μg / ml of PBNPs nanoparticles + irradiation of NIR 808nm (irradiation for 5 minutes) and 200 μg / ml of CXCR1@PBNPs nanoparticles + irradiation of NIR 808nm (irradiation for 5 minutes) were used as experimental groups. After cell stimulation, the apoptosis ratio was detected by flow cytometry. Saos2-lung osteosarcoma cells without any nanoparticles were used as a blank control group (Con).

[0066] (2) Flow cytometry

[0067] Collect cells and transfer them into flow tubes, centrifuge at 1500rpm for 5min; wash cells with PBS, centrifuge at 1500rpm for 5min; pour off supernatant, add 100μL 1× binding buffer and 5μL AnnexinⅤ staining solution according to the instructions of Becton-Dickinson Annexin V-FITC / PI kit, mix well, and incubate at room temperature for 15min; add 1μL 100μg / ml PI staining solution, and then add 400μL 1× binding buffer; detect cell binding to AnnexinⅤ and PI by flow cytometer; export data and analyze.

[0068] (3) Experimental results

[0069] The experimental results are as follows Figure 4 The results showed that the CXCR1@PBNPs nanoparticles 200 μg / ml + NIR 808 nm photothermal treatment group ( Figure 4 The CXCR1@PBNPs+NIR808 group shown in the figure can make the total apoptosis rate reach 44.28±4.09%, compared with the experimental group (PBNPs nanoparticles 200μg / ml+NIR 808nm light) Figure 4 The total apoptosis rate of the PBNPs+NIR808 group was only 32.07±2.86%, while that of the cisplatin control group ( Figure 4The total apoptosis rate of the Cis group (shown in Figure 2) was only 13.35±0.97% (P<0.001), which was statistically significant. Therefore, CXCR1@PBNPs nanoparticles have the best effect in promoting osteosarcoma cell apoptosis.

[0070] The present invention has many specific application paths, and the above is only a preferred embodiment of the present invention. It should be pointed out that the above embodiments are only used to illustrate the present invention, and are not used to limit the protection scope of the present invention. For those of ordinary skill in the art, several improvements can be made without departing from the principle of the present invention, and these improvements should also be regarded as the protection scope of the present invention.

Claims

1. A tumor-targeting nanoparticle based on CXCR1 targeting peptide and Prussian blue, It is characterized in that The tumor nanoparticles include hollow mesoporous Prussian blue nanoparticles; the surface of the hollow mesoporous Prussian blue nanoparticles is modified with a CXCR1 targeting polypeptide and the interior is loaded with a fluorescent dye; The amino acid sequence of the CXCR1 targeting polypeptide is: SAKELRCQCIKTYSKPFHPK.

2. The tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue according to claim 1, It is characterized in that The fluorescent dye is Cy7 red fluorescent dye.

3. A method for preparing tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue according to any one of claims 1 to 2, It is characterized in that The following steps are involved: S1. Synthesis of mesoporous Prussian blue nanoparticles: Polyvinyl pyrrolidone, K 3 [Fe(CN) 6 ] and HCl solution, the obtained transparent solution is heat treated, and the treated product is centrifuged and washed to obtain mesoporous Prussian blue nanoparticles; S2. Synthesis of hollow mesoporous Prussian blue nanoparticles: adding polyvinyl pyrrolidone to a PBS solution containing mesoporous Prussian blue nanoparticles, performing magnetic stirring, and then heat-treating the resulting solution under sterile conditions. The treated product is centrifuged and washed to obtain hollow mesoporous Prussian blue nanoparticles. S3. Synthesis of fluorescently labeled hollow mesoporous Prussian blue nanoparticles: dissolving the hollow mesoporous Prussian blue nanoparticles in a PBS solution, adding fluorescent dye to the resulting solution, stirring evenly, centrifuging, washing, and freeze-drying to obtain fluorescently labeled hollow mesoporous Prussian blue nanoparticles; S4. Synthesis of tumor nanoparticles based on CXCR1 targeting peptide and Prussian blue: amino groups are modified on the surface of fluorescently labeled hollow mesoporous Prussian blue nanoparticles, and the CXCR1 targeting peptide is carboxylated. The obtained amino-modified nanoparticles are combined with the carboxylated CXCR1 targeting peptide, and freeze-dried to obtain tumor nanoparticles based on CXCR1 targeting peptide and Prussian blue.

4. The method for preparing tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue according to claim 3, It is characterized in that In step S1, the heat treatment condition is: treatment at 80° C. for 24 hours.

5. The method for preparing tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue according to claim 3, It is characterized in that In step S2, the conditions for heat treatment under sterile conditions are: treatment at 140° C. for 4 hours.

6. Use of the tumor nanoparticles based on CXCR1 targeting polypeptide and Prussian blue according to any one of claims 1 to 2 in the preparation of a drug for treating osteosarcoma.

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