Targeting nanoparticle for breast cancer treatment and preparation and application thereof

Abstract

The invention discloses targeted nanoparticles for breast cancer treatment as well as preparation and application thereof, and belongs to the technical field of biological medicines. The invention provides a three-mode synergistic anti-tumor strategy of chemotherapy-photothermal therapy-Fenton-like reaction mediated ferroptosis for the first time. The targeting nanoparticles are efficiently enriched in 4T1 breast cancer cells by virtue of the dual-targeting effect of the ET peptide and the EPR; in combination with photothermal therapy, the chemotherapy effect of PTX is remarkably enhanced, and proliferation, invasion and metastasis of tumor cells are effectively inhibited. Proteomics analysis finds that differential proteins are mainly enriched in motor proteins and ferroptosis pathways after intervention of the targeted nanoparticles, and a core mechanism of collaborative treatment is disclosed. Molecular docking proves that PTX and a key target protein receptor have specific interaction, and the multi-mode synergistic strategy provides an innovative technical platform for overcoming the limitation of traditional chemotherapy and developing an efficient and low-toxicity breast cancer treatment scheme.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, and more specifically to a targeted nanoparticle for breast cancer treatment, its preparation, and its application. Background Technology

[0002] Currently, clinical treatments for breast cancer mainly include radiotherapy, surgery, and chemotherapy. Surgery is a necessary local treatment for early-stage breast cancer, but it is highly invasive and difficult to completely remove small lesions and metastases. Radiotherapy, while effective for local control, causes significant damage to normal tissues, easily leading to functional impairment. Chemotherapy, as the standard non-surgical treatment for breast cancer, especially with paclitaxel-based drugs, is widely used clinically. However, traditional chemotherapy faces serious challenges. Studies have reported that albumin-bound paclitaxel nanoparticles show improved efficacy compared to solvent-based paclitaxel monotherapy in breast cancer patients, but the objective response rate remains at 33%, and the reported number of single adverse events exceeds 20% in both groups. This indicates that existing drug delivery systems generally suffer from poor biocompatibility, insufficient long-term safety, high manufacturing costs, and limited targeting efficiency. Therefore, developing a novel nanomedicine delivery system with high targeting, high biocompatibility, and high therapeutic responsiveness is crucial for overcoming the bottlenecks in breast cancer treatment, improving efficacy, and reducing toxic side effects.

[0003] Metal-organic frameworks (MOFs) are a class of porous hybrid materials formed by the self-assembly of metal clusters / ions and organic ligands through coordination bonds, showing great potential in the field of drug delivery. Among them, the zeolite imidazole ester framework material ZIF-8 is a non-toxic and biocompatible porous material constructed from zinc ions and 2-methylimidazole through coordination interactions. It exhibits excellent biocompatibility and pH-responsive degradation characteristics: it is structurally stable in a physiologically neutral environment (pH 7.4), while in the slightly acidic environment of tumors (pH 4.5-6.5), the 2-methylimidazole protonates, leading to framework dissociation, thereby achieving intelligent controlled drug release. This characteristic makes it an ideal carrier for constructing tumor microenvironment-responsive drug delivery systems. Nevertheless, relying solely on ZIF-8 for pH-responsive drug release still faces the challenge of insufficient delivery efficiency due to the physiological barriers of tumor tissue. To overcome this obstacle, combination therapy strategies have attracted attention. Photothermal therapy (PTT) converts light energy into heat energy, locally raising the temperature of tumors. This not only directly kills tumor cells but also enhances vascular permeability and improves drug penetration, thus producing a synergistic effect with chemotherapy. Polydopamine (PDA), a biopolymer with strong absorption in the near-infrared region, is an excellent photothermal conversion agent. Furthermore, studies have shown that LRG1 (Leucine-Rich Alpha-2-Glycoprotein 1) is highly expressed in various malignant tumors, including breast cancer, and is closely related to tumor angiogenesis, epithelial-mesenchymal transition, and progression, making it a potential tumor diagnostic biomarker and therapeutic target. The ET peptide, screened using phage display technology, exhibits high affinity for LRG1, demonstrating good active targeting ability and biosafety, providing a new molecular tool for constructing precision delivery systems. Using phage display technology, a polypeptide with high affinity for LRG1—the ET peptide—was screened. Its high affinity for LRG1 and strong active tumor targeting ability were detected at the molecular, cellular, and animal levels, while the ET peptide also exhibited good biosafety.

[0004] In summary, although smart carriers such as ZIF-8 (pH-responsive), photothermal therapeutic agents, and active targeting molecules have been studied, these technologies are mostly used in isolation or simply superimposed, achieving only single drug controlled release, single thermotherapy, or single targeted modification. There is still no integrated design scheme that can integrate and synergistically regulate active targeting, smart drug release, physical thermotherapy, and induced deep biochemical killing mechanisms (such as ferroptosis). Summary of the Invention

[0005] Addressing the technical bottlenecks in current breast cancer treatments, such as low targeting efficiency of chemotherapy drugs, insufficient biocompatibility of carriers, and the tendency for drug resistance to single treatment modalities, which result in limited efficacy and significant toxic side effects, this invention aims to provide a targeted nanoparticle for breast cancer treatment, as well as its preparation and application. This targeted nanoparticle, by constructing pH-responsive, dual-targeting nanoparticles loaded with paclitaxel, achieves a synergistic effect of chemotherapy and photothermal therapy, providing a potential novel treatment strategy for breast cancer and promoting the technological development of combination therapies in tumor treatment.

[0006] To achieve the above objectives, the present invention employs the following technical solution: This invention provides targeted nanoparticles for breast cancer treatment, wherein the nanoparticles have a core-shell structure and include: Metal-organic framework nanoparticle cores loaded with chemotherapy drugs; A polydopamine layer coating the surface of the metal-organic framework nanoparticles; And a targeting peptide modified on the outer surface of the polydopamine layer by covalent linking, the targeting peptide being able to specifically bind to the LRG1 protein; The metal-organic framework material is a material with pH-responsive degradation characteristics; the polydopamine layer enables the nanoparticles to absorb near-infrared light.

[0007] The chemotherapy drugs are paclitaxel, doxorubicin, or cisplatin.

[0008] Preferably, the chemotherapy drug is paclitaxel.

[0009] The metal-organic framework material is ZIF-8.

[0010] The targeting polypeptide is the amino acid sequence of the ET polypeptide as shown in SEQ ID NO.1, or a conserved variant thereof having LRG1 targeting function.

[0011] Preferably, the amino acid sequence of the ET polypeptide is ESYSAKHRIMLT.

[0012] The targeted nanoparticles have a particle size of 200~350nm and a zeta potential of -30 mV to -50 mV.

[0013] The drug release rate of the targeted nanoparticles in a buffer solution with pH 5.0-6.5 was significantly higher than that in a buffer solution with pH 7.4.

[0014] This invention provides a method for preparing targeted nanoparticles for breast cancer treatment, comprising: Step 1: Chemotherapy drugs and metal-organic framework materials are stirred in methanol in the dark to obtain drug-loaded nanoparticles; Step 2: On the surface of the drug-loaded nanoparticles, nanoparticles with a polydopamine coating are formed by the oxidative polymerization reaction of dopamine. Step 3: The targeting peptide is covalently grafted onto the surface of the polydopamine coating layer via a carbodiimide-mediated coupling reaction to obtain targeted nanoparticles for breast cancer treatment.

[0015] The mass ratio of the chemotherapy drug to the metal-organic framework material is 1~2:1, and the mixture is stirred at room temperature for 10~14h.

[0016] The mass ratio of dopamine to drug-loaded nanoparticles is 1:1~2, and the oxidative polymerization reaction is carried out at room temperature in the dark with stirring for 10~14h.

[0017] The mass ratio of the targeted peptide to the nanoparticles is 1:(1~2), and the mixture is stirred at room temperature for 10~14h.

[0018] The present invention provides a pharmaceutical composition comprising the aforementioned targeted nanoparticles for the treatment of breast cancer, and a pharmaceutically acceptable carrier.

[0019] This invention provides the application of the aforementioned targeted nanoparticles for breast cancer treatment in the preparation of drugs for breast cancer treatment.

[0020] Preferably, the breast cancer is triple-negative breast cancer cell 4T1.

[0021] The drug is a drug that achieves synergistic treatment in combination with photothermal therapy; and / or, the drug is a drug that inhibits the proliferation of breast cancer cells by inducing ferroptosis in tumor cells.

[0022] Compared with the prior art, the present invention achieves the following technical effects: This invention provides targeted nanoparticles for breast cancer treatment. These nanoparticles utilize a core-shell structure as their overall framework, clearly defining the functions of the core and shell to optimize drug delivery. The metal-organic framework nanoparticle core, loaded with chemotherapeutic drugs, efficiently contains the drugs, providing a stable drug carrier, reducing drug loss during delivery, and protecting drug activity. A polydopamine layer coating the surface of the metal-organic framework nanoparticles forms a protective barrier, enhancing the physicochemical stability of the nanoparticles and serving as a functionalization platform for subsequent modification. The LRG1 targeting molecule specifically recognizes breast cancer-related biomarkers, achieving active targeting of tumor sites and significantly improving the accumulation capacity of the nanoparticles in the lesion area. The LRG1 targeting molecule is covalently linked to the outer surface of the polydopamine layer, ensuring firm adhesion, preventing detachment during blood circulation, and maintaining the continuity of targeting function. The chemotherapeutic drugs used for breast cancer treatment ensure therapeutic specificity, directly acting on the target disease. These features work synergistically: the core-shell structure supports the drug-loading function of the core, the polydopamine layer acts as an intermediate layer to stably connect the core and the targeting molecule, and the LRG1 targeting molecule precisely guides the nanoparticles to the tumor site, thereby jointly improving targeting efficiency, reducing non-specific effects on normal tissues, reducing systemic toxicity, and improving carrier safety by utilizing biocompatible materials.

[0023] Furthermore, pH 5.0-6.5 corresponds to the typical acidic microenvironment of tumor endosomes / lysosomes. This pathological characteristic is an inherent property of breast cancer tissue. Utilizing this range as a trigger point ensures that the drug release mechanism is highly matched with the physiological state of the tumor site, thereby avoiding non-specific activation in normal tissues. pH 7.4, as a representative value of the normal physiological environment, maintains a low drug release rate under this condition, effectively inhibiting drug diffusion in healthy tissues and reducing the risk of systemic toxicity. The release rate is significantly higher than that of the differential design, stemming from the inherent characteristic of metal-organic framework materials to rapidly protonate and break coordination bonds under acidic conditions. This response is actively regulated through the optimization of the core-shell structure, the synergistic effect of the stability of the polydopamine layer and the acid sensitivity of the metal-organic framework, enabling the drug to rapidly reach an effective concentration in the tumor microenvironment while maintaining a stable state in a neutral environment. Ultimately, this enhances the local efficacy of the chemotherapy drug and ensures the biosafety of the delivery system.

[0024] The pharmaceutical composition provided by this invention integrates targeted nanoparticles with a pharmaceutically acceptable carrier, solving the core problem of balancing targeting precision and biosafety in practical clinical applications of nanomedicine delivery systems. This provides a feasible formulation for breast cancer treatment. The targeted nanoparticles, as the core component, provide specific recognition and delivery capabilities for breast cancer, reducing non-specific drug distribution in non-target tissues and enhancing effective drug accumulation in the tumor region. The pharmaceutically acceptable carrier ensures the physicochemical stability, biocompatibility, and safe administration characteristics of the composition, enabling stable drug delivery and maintaining therapeutic activity via conventional routes. The synergistic effect of both combines the precise delivery advantage of the targeted nanoparticles with the protective and supportive function of the carrier, overcoming the deficiencies of existing delivery systems in terms of biocompatibility, targeting efficiency, and clinical safety, achieving a highly effective and low-toxicity therapeutic goal.

[0025] The application provided by this invention enhances the drug accumulation at the lesion site by leveraging the targeting properties of nanoparticles, while its design specifications ensure the stability and responsiveness of the delivery system, thereby systematically solving the problems of insufficient targeting efficiency and excessive systemic toxicity at the drug preparation level.

[0026] Furthermore, by designing drugs prepared from targeted nanoparticles for combined use with photothermal therapy, the bottlenecks of drug resistance and efficacy in the treatment of breast cancer with monotherapy were effectively addressed. The core-shell structure of the targeted nanoparticles contains a polydopamine layer, which can efficiently absorb light energy and convert it into localized heat energy under near-infrared light irradiation, thereby generating a controllable thermal effect at the tumor site. This disrupts the tumor cell membrane structure and key proteins, inducing apoptosis or necrosis. Simultaneously, the metal-organic framework core of the nanoparticles responsively degrades and releases chemotherapeutic drugs in the acidic tumor microenvironment, creating a spatiotemporal synergy between the photothermal effect and drug release. This combined mechanism not only enhances the direct killing effect on tumor cells but also increases tumor tissue permeability through the thermal effect, promoting the penetration and accumulation of chemotherapeutic drugs in the lesion area. This overcomes the drug resistance problem easily caused by monotherapy and avoids the toxic side effects caused by over-reliance on high-dose drugs. Ultimately, this design fully utilizes the inherent material properties of nanoparticles to achieve complementary synergistic effects between chemotherapy and photothermal therapy, providing a more efficient treatment pathway for breast cancer. By combining the pH-responsive release properties of nanoparticles with the targeting function of LRG1, this drug is specifically activated in the acidic tumor microenvironment, ensuring that the ferroptosis process is efficiently initiated at the lesion site. This not only enhances the depth of cell killing but also reduces the risk of systemic toxicity, providing a new strategy for overcoming the problems of high recurrence rate and poor prognosis in breast cancer. Attached Figure Description

[0027] Figure 1These are SEM and TEM images of ZIF-8, ZIF / PTX, Z / PTX-PDA, and Z / PTX-PDA-ET NPs before and after composite formation in this invention; Figure 2 The images shown are atomic force transmission electron microscope (AFM) images of the Z / PTX-PDA-ET NPs of this invention; where a is the phase image, b is the height image, and c is the 3D image. Figure 3 Infrared spectra of ZIF-8, ZIF / PTX, Z / PTX-PDA and Z / PTX-PDA-ET NPs of the present invention; Figure 4 The N2 isothermal adsorption-desorption curves and X-ray diffraction patterns of ZIF-8, ZIF / PTX, Z / PTX-PDA and Z / PTX-PDA-ET NPs of the present invention are shown in Figure a. The N2 isothermal adsorption-desorption curve is shown in Figure b. Figure 5 These are temperature-increasing images of Z / PTX-PDA-ET NPs at different concentrations according to the present invention. a is an infrared thermogram; b is a time-temperature curve. Figure 6 The images show the temperature rise of Z / PTX-PDA-ET NPs under different power laser irradiation. a is an infrared thermogram, and b is a time-temperature curve. Figure 7 Photothermal heating curves and photothermal stability cycling tests of Z / PTX-PDA-ET NPs and PDA NPs are shown. a) Comparison of temperature-time curves of the two nanoparticles, b) Five-cycle heating-cooling curves of Z / PTX-PDA-ET NPs. Figure 8 Results of hemolysis assay for Z / PTX-PDA-ET NPs; Figure 9 The cytotoxicity of ZIF-8, ZIF / PTX, Z / PTX-PDA and Z / PTX-PDA-ET NPs to 4T1 cells; Figure 10 The effect of nanoparticles on cell scratch healing (*P<0.05, ****P<0.0001, ±s, n=3, scale bar: 200 µm), a is cellular scratch; b is scratch healing rate. Figure 11 To evaluate the inhibitory effect of drug-loaded nanoparticles and photothermal therapy on 4T1 cell migration in a Transwell assay (****P<0.0001, ±s, n=3, scale bar: 100 µm); Figure 12To evaluate the inhibitory effect of drug-loaded nanoparticles and photothermal therapy on the invasive ability of 4T1 cells in a Transwell assay (****P<0.0001, ±s, n=3, scale bar: 100 µm); Figure 13 The production of ROS and Fe by co-incubating different groups of nanoparticles with 4T1 cells 2+ Fluorescence images, a is the fluorescence image of ROS production, b is the fluorescence image of Fe production. 2+ Fluorescence images; Figure 14 To analyze the ROS generation of 4T1 cells after different treatments using flow cytometry; Figure 15 Mitochondrial membrane potential fluorescence images of different groups of nanoparticles (scale bar: 100 µm). Figure 16 Fluorescence images of Z / PTX-PDA NPs and Z / PTX-PDA-ET NPs incubated with 4T1 cells for different times; Figure 17 Immunofluorescence staining images of 4T1 cells for mesenchymal cell markers vimentin, N-cadherin, and epithelial cell marker E-cadherin; Figure 18 Immunofluorescence staining images of 4T1 cells for glutathione peroxidase (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11) (scale bar: 100 µm). Figure 19 For proteomics results: a) Principal component analysis (PCA) score plot after Z / P-PDA-ET+NIR NPs treatment; b) Volcano plot of differentially expressed proteins; c) Clustering heatmap of differentially expressed proteins; d) Bar chart of KEGG functional classification of differentially expressed proteins; e) Bubble chart of KEGG enrichment analysis of differentially expressed proteins; f) Clustering heatmap of KEGG pathway-related motor proteins and ferroptosis proteins. Figure 20 Changes in blood routine parameters and biochemical indicators (mean ± standard deviation, n=3) in Balb / c mice after intraperitoneal injection of physiological saline (control) and Z / PTX-PDA-ET NPs. a: ALP level change over time; b: ALT level change over time; c: AST level change over time; d: CK level change over time; e: CREA level change over time; f: Changes in blood routine biochemical indicators. Figure 21After injection of Saline, Z / PTX-PDA NPs, and Z / PTX-PDA-ET NPs, under 808 nm laser irradiation (1.0 W / cm²), 2 (10 min) Tumor area, a is infrared thermogram, b is temperature rise curve; Figure 22 Tumor growth curves and tumor weight change curves of 4T1 tumor-bearing mice treated with different treatment groups are shown. a is the tumor growth curve and b is the tumor weight change curve. Figure 23 Representative images of the resected tumor taken on day 10 (mean ± standard deviation) ±s, n = 4); Figure 24 Images of H&E, TUNEL, Ki67, DHE and GPX4 antibody staining in tumor tissues of each treatment group (scale bar: 100 µm). Figure 25 H&E staining images of major organs in Balb / c mice from different treatment groups 18 days after treatment; Figure 26 The expression levels of E-Cadherin, N-Cadherin, and GPX4 in tumor tissues from each treatment group were detected using Western blotting. ±SEM, n=3); Figure 27 The results show the molecular docking of PTX with E-Cadherin, N-Cadherin, Vimentin, GPX4, FTH1, SLC7A11, and LRG1. Figure 28 A diagram illustrating the mechanism by which the ZIF-8 / PTX-PDA-ET nanosystem induces tumor ferroptosis. Detailed Implementation

[0028] To enable those skilled in the art to better understand the present invention, the technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings of the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort should fall within the scope of protection of the present invention.

[0029] For experiments not specifically described in the examples, the procedures or conditions should be followed according to the conventional experimental procedures described in the literature in this field. Reagents or instruments whose manufacturers are not specified are all commercially available conventional reagent products.

[0030] The ET peptide used in this invention (purchased from Jier Biochemical (Shanghai) Co., Ltd., model 1242182 (product number), with a purity >95%).

[0031] Example 1 This embodiment provides targeted nanomaterials based on metal-organic frameworks (MOFs). Paclitaxel (PTX), polydopamine (PDA), and ET peptide are simultaneously encapsulated and modified onto the surface of ZIF-8 to form nanoparticles using a one-pot method and a carbodiimide method. The specific steps are as follows: (1) Preparation of ZIF-8 NPs: A mixture of 262 mg zinc nitrate and 656 mg 2-methylimidazole was placed in a 50 mL Erlenmeyer flask, and 10 mL methanol was added. The mixture was stirred at room temperature for 20 min to obtain a white mixture, namely ZIF-8 NPs. The mixture was then centrifuged (12000 rpm, 5 min) to remove the supernatant. The resulting precipitate was immersed in 10 mL chloroform and left for 5 days to allow the residual methanol to be exchanged with the chloroform, which also helps to eliminate any unreacted substances. Finally, the ZIF-8 NPs were placed in a vacuum drying oven at 65 °C to ensure complete removal of any residual solvent.

[0032] (2) Preparation of ZIF / PTX NPs: 5 mg ZIF-8 NPs prepared above were mixed with 10 mg PTX, 10 ml methanol was added, and the mixture was stirred at room temperature in the dark for 12 h. After centrifugation to remove the supernatant, ZIF / PTX NPs were obtained.

[0033] (3) Preparation of Z / PTX-PDA NPs: 10 mg ZIF / PTX NPs were mixed with 10 mg dopamine (DA), and 10 ml tris (pH 8.5) was added. The mixture was stirred at room temperature in the dark for 12 h. After centrifugation and removal of supernatant, ZIF / PTX-PDA NPs were obtained.

[0034] (4) Preparation of Z / PTX-PDA-ET NPs: 10 mg of ET peptide (ESYSAKHRIMLT, as shown in SEQ ID NO.1) was mixed with 24 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC / HCl) and 12 mg of N-hydroxysuccinimide (NHs), and 10 ml of methanesulfonate (MES) buffer (pH 5.5) was added. The mixture was stirred at room temperature for 3 h. After activation of the ET peptide, triethylamine (TEA) was added and titrated to pH 8.0. Then, 20 mg of ZIF / PTX-PDA NPs were dissolved in the above solution and stirred at room temperature in the dark for 12 h. The supernatant was removed by centrifugation to obtain the final product Z / PTX-PDA-ET NPs.

[0035] 2. Performance Characterization (1) Morphological characteristics Small amounts of ZIF-8, ZIF / PTX, Z / PTX-PDA, and Z / PTX-PDA-ET NPs powders were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) elemental mapping, atomic force microscopy (AFM), powder X-ray diffraction (XRD), and Zeta potential metering. Detailed results are shown in the appendix. Figures 1-2 As shown.

[0036] SEM characterization analysis revealed that ZIF-8 exhibited a highly regular cubic morphology with a smooth surface and sharp edges, free from obvious defects or damage. However, after composite formation, fine particles appeared on the ZIF-8 surface. This is because, during the reaction, paclitaxel molecules, while attempting to enter the specific pore size and channel structure of ZIF-8, were limited by the pore size. Some paclitaxel molecules could not smoothly enter the pores and could only accumulate near the ZIF-8 surface. When these surface-accumulated paclitaxel molecules reached a certain concentration, they formed fine particles. TEM images of Z / PTX-PDA-ET NPs showed a uniform contrast distribution, indicating that PDA molecules were successfully encapsulated within the ZIF-8 channels without significant aggregation. The Z / PTX-PDA-ET NPs shifted from an initial cubic shape to a more spherical shape. This is because the PCM peptides, after adsorbing onto the ZIF-8 surface through electrostatic interactions, altered the surface energy of ZIF-8. To reduce surface energy, ZIF-8 crystals tended to adjust their morphology to minimize surface area. Driven by this force, the originally cubic morphology with sharp edges gradually transforms into a circle. This is because a circle has a relatively small surface area to volume ratio, which reduces surface energy and thus makes the system more stable. Combined with EDS elemental mapping, Zn, C, O, and N elements are uniformly distributed, and PDA characteristic elements (such as O and N) exhibit co-localization within the cube, confirming the effective drug loading. Furthermore, the mass ratio of sulfur increases from 0% to a final 8.07%, also indicating successful loading of the ET peptide (e.g., ...). Figure 1 In addition, atomic force microscopy (AFM) Figure 2 (a) visually reflects the varying degrees of roughness on the surface of Z / PTX-PDA-ET NPs, indicating that drug or peptide modification or structural alteration has led to increased surface inhomogeneity. AFM ( Figure 2 (b) provides nanometer-level spatial resolution, clearly observing the morphology and size of individual Z / PTX-PDA-ET NPs. It can be seen that the Z / PTX-PDA-ET NPs are relatively uniform in size and exhibit a certain degree of aggregation. AFM ( Figure 2c) The height at different locations on the sample surface was accurately measured. The thickness of Z / PTX-PDA-ET NPs was not very uniform, and the peptides caused new surface undulations on the ZIF-8 surface. (2) Analysis of particle size, zeta potential, encapsulation efficiency and drug loading The standard curve for paclitaxel determination using high-performance liquid chromatography (HPLC) was Y = 38.648 + 147.404. When the ZIF to PTX ratio was 1:2, the calculated encapsulation efficiency (EE) of PTX was 96.9%, and the drug loading (DLC) was 54.3%. The ability of Z / PTX-PDA-ET NPs to release PTX under different pH conditions was further evaluated using ultraviolet spectrophotometry. The release of PTX from the ZIF-8 structure was pH-dependent. At pH 5.5, the cumulative release of PTX from Z / PTX-PDA-ET reached 40% within 35 minutes; at pH 7.4, the cumulative release was only 30%, indicating that PTX is relatively stable under neutral conditions. Therefore, given the weakly acidic tumor microenvironment, the pH-responsive release of PFDs will be beneficial for the application of Z / PTX-PDA-ET NPs in disease treatment.

[0037] The particle size of Z / PTX-PDA-ET NPs is 310.81 nm, which is much larger than that of hollow ZIF-8 NPs (126.18 nm). This is because the modification of hollow ZIF-8 NPs with PTX, PDA, and ET peptides increases the size of ZIF-8 NPs. The modification also leads to the aggregation of nanoparticles, which increases the particle size (as shown in Table 1).

[0038] Table 1: Hydration particle size, PDI, and Zeta potential of ZIF-8, ZIF / PTX, Z / PTX-PDA, and Z / PTX-PDA-ET NPs

[0039] To verify the stability of Z / PTX-PDA-ET NPs, they were prepared into a suspension and placed in a 4°C refrigerator. The particle size distribution was detected at different time points. The results showed that no significant particle size change occurred in Z / PTX-PDA-ET NPs within 28 days, proving that the prepared Z / PTX-PDA-ET NPs have good stability.

[0040] The Zeta potentials of ZIF-8, ZIF / PTX, Z / PTX-PDA, and Z / PTX-PDA-ET NPs were 39.66 mV, 32.31 mV, -16.86 mV, and -42.86 mV, respectively. Among them, ZIF-8 had a larger absolute value of Zeta potential, indicating its relative stability in solution and resistance to aggregation. Furthermore, a small amount of drug in the drug-loaded ZIF-8 was adsorbed onto the nanoparticle surface through strong adsorption, resulting in a slightly lower Zeta potential for ZIF / PTX NPs compared to the blank ZIF-8. Due to the presence of hydroxyl and carboxyl groups in PDA-ET, the Zeta potential of Z / PTX-PDA NPs became negative after PDA coating, while the potential of Z / PTX-PDA-ET NPs was even lower. This significant decrease in Zeta potential confirms the successful adsorption of PDA-ET. The negative surface charge of the nanoparticles prolongs their circulation in the blood, thereby reducing any cytotoxicity caused by the proton sponge effect.

[0041] (3) Infrared spectroscopy analysis The infrared spectra of ZIF / PTX, Z / P / PDA, and Z / P / PDA-ET nanoparticles are as follows: Figure 3 As shown. Compared to ZIF-8, the 1735 cm⁻¹ infrared spectrum of ZIF / PTX... -1 The absorption peak appearing at 1703 cm⁻¹ is attributed to the stretching vibration of the carbonyl C=O group in PTX. The Z / P / PDA peak at 1703 cm⁻¹ is also relevant. -1 The absorption peak appearing at 638 cm⁻¹ is attributed to the stretching vibration of the CN bond in the PDA. The Z / P / PDA absorption peak at 638 cm⁻¹ is also relevant. -1 The absorption peak observed is attributed to the bending vibration of the CH bond in the ET peptide. This indicates that PTX was successfully encapsulated within ZIF-8 nanoparticles, and that PDA and the ET peptide were successfully composited on the ZIF-8 nanoparticles. This is because the amino group on NH2-PEG can undergo Mike addition or Schiff base reaction with the quinone structure on PDA, thereby linking the ET peptide to the PDA layer.

[0042] (4) BET analysis Nanomaterials with different encapsulation treatments were tested using a BET analyzer. (See...) Figure 4 As shown in Figure a, the results show that the ZIF-8 material has a specific surface area and pore volume of 1,705.5491 m². 2 / g and 0.611725 cm 3 / g, with a pore size of 77.87925 nm. Further modification yielded Z / PTX-PDA NPs of 20.3872 m. 2 / g and 0.001044cm 3The nanoparticles, with a pore size of 61.24155 nm, exhibited minimal size variation. However, both their specific surface area and pore capacity decreased significantly, indicating that the internal pores were filled by PTX and PDA. Through the linkage of ET peptides, the specific surface area of ​​the nanoparticles decreased again, while the pore capacity increased to 9.4828 nm. 2 / g and 0.002015 cm 3 / g, with a pore size of 76.7452 nm. Based on the aforementioned results, zif-90 with a pore size of 1.6267 nm was successfully synthesized and successfully loaded with PTX and PDA. By linking ET peptides, significant changes were observed in the specific surface area, pore capacity, and pore size of the nanomaterial. This is attributed to various modifications made to the Z / PTX-PDA-ET NPs, further indicating the successful preparation of the material.

[0043] (5) XRD analysis In X-ray electron diffraction analysis of nanoparticles, the nitrogen adsorption amount of nanoparticles encapsulated with polydopamine and adsorbed with ET peptides decreased, indicating that polydopamine and ET peptides had modified the nanoparticle surface. Furthermore, in specific surface area analysis, after successive modification with polydopamine and ET peptides, the diffraction peaks decreased to some extent, but both retained the same characteristic diffraction peaks as ZIF-8 and ZIF / PTX. Therefore, the functionalization modification of the ZIF-8 paclitaxel particle surface does not affect the modified crystal structure (e.g., ...). Figure 4 (As shown in b).

[0044] (6) Photothermal performance Temperature curves of different concentrations of Z / PTX-PDA-ET NPs versus time were obtained in vitro, as shown below. Figure 5-6 As shown, the solution temperature gradually increased with increasing nanoparticle concentration and irradiation time. The control group solution showed little temperature change under laser irradiation; however, when the nanoparticle concentration increased to 5 mg / mL, the temperature of the Z / PTX-PDA-ET NPs aqueous solution rose from 26.7℃ to 52.9℃. In vitro laser power density versus time-temperature curves showed that the temperature increase became more pronounced with increasing laser power density, indicating that under the same nanoparticle concentration and laser power density, the temperature-time curves of Z / PTX-PDA-ET NPs and PDA NPs were highly consistent, suggesting that drug loading and ET peptide linkage did not affect the thermogenic effect of PDA NPs. After repeated laser irradiation and five cycles of heating and cooling, Z / PTX-PDA-ET NPs exhibited similar temperature curves in each cycle, indicating stable photothermal properties (see...). Figure 7 ).

[0045] (7) Hemolysis test The blood compatibility of the Z / PTX-PDA-ET nanocarrier was verified by hemolysis experiments. Experimental data showed that when the concentration of nanoparticles was in the high-dose range of 1-5 mg / mL ( Figure 8 The hemolysis rate remained consistently below the international safety threshold of 5%, and no significant red blood cell rupture was observed. Among them, the hemolysis rate of 5 mg / mL Z / PTX-PDA-ET NPs was 1.24%, which can be considered as having very low toxicity to the body.

[0046] Example 2 Based on Example 1, this embodiment characterizes the nanoparticles prepared by the present invention in vitro, mainly examining their effects on cytotoxicity, cell scratch healing, cell migration and invasion, ROS generation, mitochondrial membrane potential, cell uptake, and cell immunofluorescence.

[0047] (1) Cytotoxicity test Cytotoxicity assays were performed using ZIF-8, ZIF / PTX, Z / PTX-PDA, and Z / PTX-PDA-ET NPs. Results are as follows: Figure 9 As shown in the figure, when the ZIF-8 NP concentrations were 6.25, 12.5, 25, 50, and 100 μg / mL, the cell viability of the ZIF-8 group did not change significantly, indicating that the material was essentially non-toxic to cells. When the ZIF / PTX, Z / PTX-PDA, and Z / PTX-PDA-ET NP concentrations were 6.25, 12.5, 25, 50, and 100 μg / mL, all three groups showed varying degrees of toxicity to 4T1 cells. With increasing concentration, the toxicity of all four groups to 4T1 cells gradually increased. Furthermore, the toxicity of each concentration of the Z / PTX-PDA-ET group to MCF-7 cells was slightly higher than that of the other three groups. Encapsulation with PTX, PDA, and ET peptides effectively improved their lethality against tumor cells.

[0048] (2) Effect on cell scratch healing Compared with the control group, the ZIF / PTX-PDA group showed weak inhibitory effect on cell healing ability. The scratch healing rates of the Z / PTX-PDA-ET, Z / PTX-PDA+NIR, and Z / PTX-PDA-ET+NIR groups were all significantly reduced (P < 0.01), with the Z / PTX-PDA-ET+NIR group showing virtually no healing ability. The Z / PTX-PDA-ET+NIR group showed a significantly stronger inhibitory effect on 4T1 cell healing ability than the other three groups (P < 0.01). No significant difference was found between the drug-induced healing inhibition effects at 24h and 48h. This indicates that the targeting of Z / PTX-PDA-ET and near-infrared light irradiation are beneficial for the nanoparticles to inhibit tumor cell healing (e.g., Figure 10 ).

[0049] (3) Effects on cell migration and invasion like Figure 11-12 Compared to the control group, all experimental groups showed inhibitory effects on the migration and invasion of 4T1 cells. The Z / PTX-PDA-ET+NIR targeted drug group exhibited stronger inhibitory effects on migration and invasion compared to the Z / PTX-PDA+NIR non-targeted drug group, and the Z / PTX-PDA-ET+NIR photothermal therapy group showed stronger inhibitory effects on migration and invasion compared to the Z / PTX-PDA-ET non-photothermal therapy group. Therefore, the inhibitory effect on the migration and invasion of 4T1 cells is influenced by the targeting of Z / PTX-PDA-ET and near-infrared light irradiation, consistent with the results of the scratch assay.

[0050] (4) Detection of ROS generation DCFH-DA produces green fluorescence through ROS oxidation, and is therefore used to assess ROS production in 4T1 cells. Figure 13 Compared with the control group, 4T1 cells treated with Z / PTX-PDA and Z / PTX-PDA-ET groups emitted relatively strong green fluorescence signals. This is because the overexpressed H2O2 in tumor cells can react with Cu. 2+ / Cu + A small amount of •OH is generated through a Fenton-like reaction. Compared to the Z / PTX-PDA group, the fluorescence intensity of cells treated with Z / PTX-PDA-ET NPs decreased. This is because CAT can decompose intracellular H2O2, indicating that a cascade catalytic reaction can occur between GOx and CAT within the cell. Simultaneously, the ROS levels of cells treated with different samples under laser irradiation were detected. The green fluorescence of both the Z / PTX-PDA+NIR and Z / PTX-PDA-ET+NIR groups was enhanced. This is because the photothermal effect caused by 808 nm laser irradiation can improve the efficiency of CDT in generating ROS. The cells treated with Z / PTX-PDA-ET+NIR showed the strongest fluorescence intensity because CAT provides oxygen for GOx oxidation, accelerating the production of H2O2, thus leading to increased fluorescence intensity. Quantitative analysis by flow cytometry... Figure 14 The results also confirmed these findings.

[0051] (5) Detection of mitochondrial membrane potential like Figure 15 By detecting the mitochondrial membrane potential of 4T1 cells, it was found that the mitochondrial membrane potential of the Z / PTX-PDA-ET group was significantly lower than that of the Z / PTX-PDA group. Compared with the Z / PTX-PDA-ET+NIR group, the mitochondrial membrane potential of 4T1 cells irradiated with near-infrared light was also significantly lower in the Z / PTX-PDA-ET group. Therefore, the targeting and photothermal therapy of ET peptides can promote apoptosis by reducing mitochondrial membrane potential.

[0052] (6) Cellular uptake of nanoparticles The phagocytosis of Z / PTX-PDA NPs and Z / PTX-PDA-ET NPs by 4T1 cells was directly observed using CLSM. Figure 16 As shown, under laser irradiation, nanoparticles stained with DiR exhibited red fluorescence, while cell nuclei stained with DAPI showed blue fluorescence. With increasing co-culture time (0.5, 1, 2 h) between nanoparticles and cells, the red fluorescence of both the coated and uncoated groups gradually increased. Furthermore, at the same time point, the red light surrounding cells in the coated group was stronger than that in the uncoated group, indicating that Z / PTX-PDA-ETNPs possess the ability to target tumor cells.

[0053] (7) Cellular immunofluorescence LRG1 plays a crucial role in malignant tumors by promoting angiogenesis and influencing cell proliferation, differentiation, and migration. LRG1 is believed to promote pathogenic angiogenesis by facilitating the interaction between the TGF-β1 / ALK1 signaling pathway and endothelin. To verify whether this study is related to this pathway, immunofluorescence staining was performed on cells treated with different nanoparticles to detect the levels of leucine-rich α-2-glycoprotein 1 (LRG1) and transforming growth factor β1 (TGF-β1). After treatment with Z / PTX-PDA-ET and Z / PTX-PDA-ET+NIR, the fluorescence intensity of LRG1 and TGF-β1 was significantly reduced compared to the control group, ZIF / PTX-PDA group, and Z / PTX-PDA+NIR group. The fluorescence intensity decrease was more pronounced in the Z / PTX-PDA-ET+NIR group than in the Z / PTX-PDA-ET group, suggesting that LRG1 affects the formation of stromal microvessels in breast cancer by regulating the TGF-β1 signaling pathway.

[0054] Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells transform into mesenchymal cells. Epithelial cells lose their apical polarity and adhesiveness, acquiring the phenotype of mesenchymal cells and gaining the ability to migrate, thus promoting metastasis and drug resistance. To assess the effects of different treatments on the EMT process, immunofluorescence staining analysis was performed on mesenchymal cell markers vimentin, N-cadherin, and epithelial cell marker epithelial-type cadherin. In the immunofluorescence images ( Figure 17Compared with the control group and the ZIF / PTX-PDA group, the fluorescence intensity of the Z / PTX-PDA-ET group, Z / PTX-PDA+NIR group, and Z / PTX-PDA-ET+NIR group all decreased to varying degrees. In immunofluorescence staining of Vimentin, there was no significant difference between the Z / PTX-PDA-ET group and the Z / PTX-PDA-ET+NIR group, but their fluorescence intensity was lower than that of the other groups. In the fluorescence staining of N-Cadherin and E-Cadherin, the fluorescence intensity of the Z / PTX-PDA-ET+NIR group decreased more significantly than that of the Z / PTX-PDA-ET group and the Z / PTX-PDA+NIR group, suggesting that it may have a better inhibitory effect on the expression of epithelial-mesenchymal transition-related proteins, which is consistent with the Transwell assay and cell scratch healing assay.

[0055] To further investigate whether nanoparticles inhibit breast cancer progression through ferroptosis and to evaluate the effects of different treatments on ferroptosis-negative regulatory proteins, immunofluorescence staining was performed on cells treated with different nanoparticles to detect the levels of glutathione peroxidase (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11). Images show ( Figure 18 Compared to the control group and the ZIF / PTX-PDA group, the fluorescence intensities of GPX4, FTH1, and SLC7A11 in the Z / PTX-PDA-ET, Z / PTX-PDA+NIR, and Z / PTX-PDA-ET+NIR groups were significantly reduced. Furthermore, the decrease was more pronounced in the Z / PTX-PDA-ET+NIR group than in the Z / PTX-PDA-ET and Z / PTX-PDA+NIR groups, suggesting that it may have a better inhibitory effect on the expression of negative regulators of ferroptosis.

[0056] (8) Proteomics See Figure 19The enriched proteins after treatment with Z / P-PDA-ET+NIR targeted nanoparticles were detected using the 4D-DIA proteomics method. Based on bioinformatics analysis, a total of 8026 quantitatively comparable and reliable proteins were identified. Principal component analysis (PCA) showed a clear boundary between the Z / P-PDA-ET+NIR group and the control group. According to the screening criteria for differentially expressed proteins (DEPs) (fold change ≥1.5 or ≤0.6667, p<0.05), compared with the model group, 259 proteins were significantly upregulated and 212 proteins were downregulated in the Z / P-PDA-ET+NIR group. The differentially expressed proteins in the Z / P-PDA-ET+NIR group and the control group were analyzed by KEGG functional annotation and enrichment. The differentially expressed proteins (DEPs) showed significant enrichment in functions related to regulating cell death. KEGG pathway analysis revealed that the dysregulated proteins involved in motility, ferroptosis, and cytokine-receptor interactions. Significant differences were found between the Control and Z / P-PDA-ET+NIR NPs groups. Cluster heatmap analysis revealed significant differences in motor proteins and ferroptosis-related proteins between the two groups. The differentially expressed proteins were involved in the pathways of GPX4, SLC7A11, and FTH1, which is consistent with the experimental results above.

[0057] Example 3 This embodiment, based on Embodiments 1 and 2, focuses on the targeted nanoparticles of the present invention used for breast cancer treatment. (1) Evaluation of the biosafety of nanoparticles in vivo like Figure 20 The results showed that there were no significant differences in blood routine and blood biochemistry analysis between normal mice injected intraperitoneally with Z / PTX-PDA-ET NPs and the saline group. This demonstrates that the nanoparticles have high biocompatibility and no toxic side effects on the human body.

[0058] (2) In vivo therapeutic experiments with nanoparticles Figure 21 The results showed that laser irradiation (1 W / cm²) was effective. 2 After 10 min, under the monitoring of an infrared thermal imager, the temperature of the tumor site in the Z / PTX-PDA NPs+NIR group and the Z / PTX-PDA-ET+NIR group reached 44℃ and 53.7℃, respectively, indicating that the loading of the targeting peptide does not affect the photothermal effect of Z / PTX-PDA-ET NPs in vivo. Compared with Z / PTX-PDA-ET NPs and Z / PTX-PDA NPs, the heating effect of Z / PTX-PDA NPs was relatively poor. This is because the targeting effect of the ET peptide increases the aggregation of nanoparticles in the tumor.

[0059] The efficacy of this nanoparticle in synergistic chemotherapy and photothermal therapy was evaluated through in vivo observation. Figure 22, Figure 23 The conclusion was that the tumor volume increased 3.28 times in the saline treatment group, indicating rapid tumor cell growth and high malignancy. Tumor growth was inhibited in the Z / PTX-PDA and Z / PTX-PDA-ET groups under laser irradiation (P < 0.05), but the tumor volume was larger than that in the Z / PTX-PDA-ET NPs+NIR group. The Z / PTX-PDA-ET NPs group alone had a weak inhibitory effect on tumor growth; however, the combination of Z / PTX-PDA-ET NPs and laser therapy resulted in the most significant tumor growth inhibition and the smallest tumor volume (P < 0.05).

[0060] The biosafety of targeted drug-loaded nanoparticles was evaluated using a mouse model. After five injections of the drug and near-infrared light irradiation, the complete blood count and blood biochemistry results of the model mice were analyzed. The combined use of Z / PTX-PDA-ET and photothermal therapy significantly affected some indicators, specifically increasing aspartate aminotransferase (AST) and alanine aminotransferase (ALT). However, serum creatinine (CREA) showed no significant difference compared to the saline group.

[0061] See Figures 24-26 The pathological results of tumor sections from different groups showed that the tumor cells in the saline group had clear morphology and structure with no obvious apoptosis / necrosis, while the cells in all treatment groups showed varying degrees of necrosis, with the Z / PTX-PDA-ET NPs+NIR group exhibiting the most severe necrosis. Ki67 antibody staining to detect tumor cell proliferation indicated that the Z / PTX-PDA-ET NPs+NIR group had the least tumor cell proliferation. Furthermore, TUNEL apoptosis analysis showed that the Z / PTX-PDA-ET NPs+NIR group had the most severe apoptosis and necrosis. However, H&E staining analysis of the major organ tissues of the mice showed no histological abnormalities, indicating that the biomimetic nanoparticles had no toxic side effects on normal tissues and only had a killing effect on tumors. In addition, GPX4 ferroptosis antibody staining showed that ferroptosis regulatory proteins were downregulated in the Z / PTX-PDA-ET NPs+NIR group, indicating that the promotion of apoptosis by Z / PTX-PDA-ET NPs+NIR NPs is related to ferroptosis.

[0062] Example 4 See Figure 27The CB-Dock2 software was used to perform molecular docking between the candidate target protein and PTX. The 3D model illustrates how PTX binds to the target protein receptor and interacts with adjacent amino acid residues. Hydrogen bonds, weak hydrogen bonds, hydrophobic interactions, ionic interactions, cation-π interactions, and π-π stacking are all involved, with hydrogen bonds being the main nonionic force. By studying the molecular targets of PTX and predicting the specific binding of PTX to LRG1 (e.g., S48, L33, S32), E-Cadherin (e.g., H756, D759), N-Cadherin (e.g., E248, V247, F143, P144), Vimentin (e.g., I411, L413, F418, S419, L421), CTGF (e.g., D634, F570, S571, H525), GPX4 (e.g., D24, I23, F36), FTH1 (e.g., E148, T175, H152), and SLC7A11 (e.g., I192, F336, I52), it is shown that PTX can exert its anti-tumor effect by modifying transforming growth factor, epithelial-mesenchymal transition factor, and ferroptosis regulatory proteins, providing validation of the above mechanisms at the molecular level.

[0063] In summary, the mechanism of the targeted nanoparticles for breast cancer treatment of the present invention was analyzed, see Appendix. Figure 28 After the targeted nanoparticles enter the tumor microenvironment, Step 1: Tumor Microenvironment Response and Activation Acid-responsive release: The tumor tissue is weakly acidic (pH 5.5), leading to the disintegration of the ZIF-8 structure and the release of loaded PTX and Fe. 2+ Photothermal triggering: NIR laser irradiation generates heat in the PDA coating, further promoting drug release and enhancing the therapeutic effect.

[0064] Step 2: Triggering the core biochemical reaction of ferrodeath Iron metabolism disorder: released Fe 2+ The Fenton reaction generates a large amount of highly reactive reactive oxygen species (ROS, such as ·OH). At the same time, NCOA4 protein-mediated ferritin autophagy releases more iron ions, exacerbating oxidative stress.

[0065] The antioxidant defense system collapses: The system inhibits the SLC7A11 cysteine ​​transporter on the cell membrane. This prevents the cell from taking up cysteine ​​to synthesize glutathione. Glutathione is an essential cofactor for the core antioxidant enzyme GPX4. Inhibition of GPX4 activity prevents it from performing its function of reducing hydrogen peroxide.

[0066] Irreversible cell damage: Under the dual impact of massive ROS production and GPX4 depletion, polyunsaturated fatty acids on the cell membrane undergo lipid peroxidation. The continuous accumulation of lipid peroxidation products eventually leads to cell membrane rupture and ferroptosis.

[0067] Step 3: Synergistic Enhancement Chemotherapy drug PTX directly kills tumor cells by interfering with microtubule function. Ferrocytes disrupt cell membrane integrity and cause oxidative stress, which complements the mechanism of PTX, producing a synergistic anti-tumor effect.

[0068] This invention proposes for the first time a three-modal synergistic anti-tumor strategy involving chemotherapy, photothermal therapy, and Fenton-like response-mediated ferroptosis. The targeted nanoparticles, leveraging the dual targeting effects of ET peptide and EPR, efficiently accumulate in 4T1 breast cancer cells. Combined with photothermal therapy, this significantly enhances the chemotherapeutic effect of PTX, effectively inhibiting tumor cell proliferation, invasion, and metastasis. Proteomics analysis revealed that differentially expressed proteins after targeted nanoparticle intervention were mainly enriched in motor proteins and the ferroptosis pathway, revealing the core mechanism of the synergistic therapy. Molecular docking confirmed the specific interaction between PTX and key target protein receptors. This multimodal synergistic strategy provides an innovative technological platform for overcoming the limitations of traditional chemotherapy and developing highly effective and low-toxicity breast cancer treatment regimens.

[0069] The above content is only for illustrating the technical concept of the present invention and should not be construed as limiting the scope of protection of the present invention. Any modifications made to the technical solution based on the technical concept proposed in this invention shall fall within the scope of protection of the claims of this invention.

Claims

1. A targeted nanoparticle for breast cancer treatment, characterized in that, The nanoparticles have a core-shell structure and include: Metal-organic framework nanoparticle cores loaded with chemotherapy drugs; A polydopamine layer coating the surface of the metal-organic framework nanoparticles; And a targeting peptide modified on the outer surface of the polydopamine layer by covalent linking, the targeting peptide being able to specifically bind to the LRG1 protein; The metal-organic framework material is a material with pH-responsive degradation characteristics; the polydopamine layer enables the targeted nanoparticles to absorb near-infrared light.

2. The targeted nanoparticle for breast cancer treatment according to claim 1, characterized in that, The chemotherapy drugs are paclitaxel, doxorubicin, or cisplatin.

3. The targeted nanoparticle for breast cancer treatment according to claim 1, characterized in that, The metal-organic framework material is ZIF-8.

4. The targeted nanoparticle for breast cancer treatment according to claim 1, characterized in that, The targeting polypeptide is the amino acid sequence of the ET polypeptide as shown in SEQ ID NO.1, or a conserved variant thereof having LRG1 targeting function.

5. The targeted nanoparticle for breast cancer treatment according to claim 1, characterized in that, The targeted nanoparticles have a particle size of 200~350nm and a zeta potential of -30 mV to -50 mV.

6. The targeted nanoparticle for breast cancer treatment according to claim 1, characterized in that, The drug release rate of the targeted nanoparticles in a buffer solution with pH 5.0-6.5 was significantly higher than that in a buffer solution with pH 7.

4.

7. A method for preparing targeted nanoparticles for breast cancer treatment according to any one of claims 1-6, characterized in that, Includes the following steps: Step 1: Chemotherapy drugs and metal-organic framework materials are stirred in methanol in the dark to obtain drug-loaded nanoparticles; Step 2: On the surface of the drug-loaded nanoparticles, nanoparticles with a polydopamine coating are formed by the oxidative polymerization reaction of dopamine. Step 3: The targeting peptide is covalently grafted onto the surface of the polydopamine coating layer via a carbodiimide-mediated coupling reaction to obtain targeted nanoparticles for breast cancer treatment.

8. A pharmaceutical composition, characterized in that, The pharmaceutical composition comprises a targeted nanoparticle for the treatment of breast cancer as described in any one of claims 1-6, and a pharmaceutically acceptable carrier.

9. The use of the targeted nanoparticle for breast cancer treatment according to any one of claims 1 to 6 in the preparation of a drug for breast cancer treatment.

10. The application according to claim 9, characterized in that, The drug is a drug that achieves synergistic treatment in combination with photothermal therapy; and / or, the drug is a drug that inhibits the proliferation of breast cancer cells by inducing ferroptosis in tumor cells.

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