A pancreatic cancer deep penetration ferroptosis nano preparation and a preparation method and application thereof

Abstract

The application provides a pancreatic cancer deep penetration ferroptosis nano preparation and a preparation method and application thereof, the nano preparation comprises a drug-loaded core and a MOF shell, the drug-loaded core is formed by polymerization of a ferroptosis inducer Erastin and a polymer material, and the MOF is formed by coordination of iron ions and tannic acid. The preparation method is as follows: iron ions, the polymer material and Erastin are mixed to form an organic phase solution, the solution is slowly dropped into a tannic acid aqueous phase solution, and the nano preparation is obtained through ultrasonic and stirring. The nano preparation constructed in the application can regulate the re-polarization of tumor-associated macrophages, thereby reducing the activation and collagen deposition of tumor-associated fibroblasts to regulate the dense tumor stroma, achieving deep penetration of the nano preparation, after reaching the deep part of the tumor, the iron ions and Erastin synergistically act to destroy the redox balance of tumor cells, improve the ferroptosis effect of tumor cells, and realize ferroptosis treatment of pancreatic cancer cells.

Description

Technical Field

[0001] This invention relates to the fields of nanomaterials and nanobiomedicine, specifically to a deep-penetrating ferrodeation nano-formulation for pancreatic cancer, its preparation method, and its application. Background Technology

[0002] Pancreatic cancer is a highly fatal malignant tumor of the digestive system, with a 5-year survival rate of less than 10%. Even with the current prevalence of immunotherapy and targeted therapy, the survival rate has not improved. Currently, surgical resection remains the only chance to cure pancreatic cancer. However, chemotherapy is a crucial part of comprehensive treatment strategies for both post-operative patients and those who are not candidates for surgery at the time of diagnosis. However, pancreatic cancer responds poorly to most chemotherapy drugs. Currently, first-line drugs, primarily gemcitabine, have shown limited effectiveness. More importantly, because over 90% of pancreatic cancers have KRAS gene mutations, the cancer cells exhibit high drug resistance, resulting in no substantial improvement in patient survival and numerous adverse reactions such as bone marrow suppression. Therefore, there is an urgent need to find new comprehensive treatment strategies for pancreatic cancer to improve patient survival and address a series of problems in its clinical treatment.

[0003] Current research has found that pancreatic cancer cells, due to KRAS gene mutations, have high levels of intracellular reactive oxygen species (ROS), which enhances the accumulation of lipid peroxides, making them sensitive to ferroptosis. However, numerous studies have shown that pancreatic cancer cells possess a dense tumor matrix, accounting for 90% of the tumor volume, which acts as a physical barrier preventing effective drug delivery to the tumor site. Therefore, developing a deeply penetrating nanoparticle formulation to disrupt the redox balance of tumor cells and enhance ferroptosis is of significant clinical importance for the treatment of pancreatic cancer cells with ferroptosis. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a deep-penetrating ferroptosis nanoparticle formulation for pancreatic cancer, its preparation method, and its application. The aim is to construct a nanoparticle formulation with Erastin as its core and an MOF shell formed by iron ions and tannic acid, thereby reducing the activation of tumor-associated fibroblasts and collagen deposition to regulate the dense tumor matrix and achieve deep penetration of the nanoparticle formulation. The synergistic effect of iron ions and Erastin disrupts the redox balance of tumor cells, enhances the ferroptosis effect, and achieves ferroptosis therapy for pancreatic cancer cells.

[0005] To achieve the above objectives, the present invention first provides a deep-penetrating ferroptosis nanoformulation for pancreatic cancer. The nanoformulation includes a drug-loaded core and a MOF shell. The drug-loaded core is polymerized from the ferroptosis inducer Erastin and a polymer material. The MOF shell is formed by the coordination of iron ions and tannic acid.

[0006] Preferably, the mass ratio of Erastin to polymer material is 1:50 to 1:10.

[0007] Preferably, the molar ratio of tannic acid to iron ions is 1:10 to 10:1.

[0008] Preferably, the polymer material is any one of polylactic acid-glycolic acid copolymer, polyvinyl alcohol, and polyvinylpyrrolidone.

[0009] Preferably, the nano-formulation has a regular spherical core-shell structure with a particle size of about 70 nm and a shell thickness of about 10 nm.

[0010] Based on a general inventive concept, this invention also provides a method for preparing a deep-penetrating ferrodeation nanoparticle formulation for pancreatic cancer, comprising the following steps:

[0011] S1. Dissolve tannic acid in water and use it as the aqueous phase for later use;

[0012] S2. Add the polymer material, iron ions, and Erastin to an organic reagent and dissolve them to form the organic phase;

[0013] S3. Under ultrasonic conditions, the organic phase liquid is slowly dripped into the aqueous phase, and then stirred under constant temperature conditions in a water bath to allow the organic solvent to evaporate completely. The resulting solution is centrifuged, washed with ultrapure water, and reconstituted to obtain the deep-penetrating iron death nano-preparation agent (PTFE) for pancreatic cancer.

[0014] Preferably, the concentration ratio of polymer material, iron ions and Erastin in step S2 is 25:5:3.

[0015] Preferably, the organic reagent in step S2 is either acetone or acetonitrile.

[0016] Preferably, in step S3, the water bath temperature is 20–40°C and the stirring time is 1–6 hours.

[0017] Based on a general inventive concept, this invention also provides the application of pancreatic cancer deep-penetrating ferrode nanoformulations in the preparation of anti-pancreatic cancer drugs.

[0018] The mechanism by which this invention can alleviate pancreatic cancer is as follows:

[0019] This invention constructs a nano-formulation with Erastin as the core and an MOF shell formed by iron ions and tannic acid, which improves the solubility of Erastin and the effective drug concentration at the tumor site. The nano-formulation of this invention can regulate the repolarization of tumor-associated M2 macrophages into M1 macrophages, thereby reducing the secretion of transforming growth factor β (TGF-β) and modulating the tumor microenvironment, thus reducing the activation and collagen deposition of tumor-associated fibroblasts (TAFs). This effectively overcomes the huge barrier formed by the dense tumor matrix, achieving deep penetration of the nano-formulation. After penetrating deep into the tumor, due to the acid-sensitive nature of the nano-formulation, its structure gradually disintegrates in the tumor microenvironment. Tumor cells actively take up large amounts of iron ions, which induce the Fenton reaction, generating a large amount of reactive oxygen species (ROS). This leads to the accumulation of lipid peroxidation on the tumor cell membrane, further damaging the tumor cell membrane. This oxidative damage cannot be repaired by the cells, ultimately leading to tumor cell death. Simultaneously, Erastin, as an inducer of ferroptosis, disrupts the redox balance within tumor cells, reducing cellular antioxidant capacity and increasing intracellular ROS, achieving synergistic ferroptosis therapy in pancreatic cancer cells.

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

[0021] 1. The deep-penetrating ferrodeation nanoparticles prepared in this invention can regulate the repolarization of M2 macrophages into M1 macrophages in the pancreatic cancer microenvironment. By reducing the secretion of transforming growth factor β (TGF-β), the tumor microenvironment is regulated, thereby reducing the activation and collagen deposition of tumor-associated fibroblasts (TAFs). This effectively overcomes the huge barrier formed by the dense tumor matrix and achieves deep penetration of the nanoparticles.

[0022] 2. The deep-penetrating ferroptosis nanoparticles prepared in this invention, after penetrating deep into the tumor, induce a Fenton reaction with iron ions, generating a large amount of reactive oxygen species, leading to the accumulation of lipid peroxidation on the cell membrane. At the same time, Erastin disrupts the redox balance of tumor cells, enhances the ferroptosis effect of tumor cells, and achieves synergistic ferroptosis therapy for pancreatic cancer cells.

[0023] 3. The deep-penetrating iron death nanoparticles prepared by this invention have uniform particle size and good stability. Attached Figure Description

[0024] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0025] Figure 1Transmission electron microscopy image (scale bar 50 nm) of the deep-penetrating iron-death nano-formulation in Experimental Example 1 of this invention;

[0026] Figure 2 The elemental analysis diagram (scale bar 30 nm) of the deep-penetrating iron-death nano-formulation in Experimental Example 1 of this invention is shown.

[0027] Figure 3 Stability analysis of the deep-penetrating iron-death nano-formulation in Experimental Example 1 of this invention;

[0028] Figure 4 For the acid sensitivity analysis of the deep-penetrating iron-death nano-formulation in Experimental Example 1 of this invention, Figure 4 A represents the cumulative release curve of Erastin. Figure 4 B is a transmission electron microscope image of the nano-formulation after incubation at pH 7.4. Figure 4 C is a transmission electron microscope image of the nano-formulation after incubation at pH 5.5;

[0029] Figure 5 This is the result of the Fenton effect in the deep-penetrating iron-death nano-formulation of Experimental Example 1 of the present invention;

[0030] Figure 6 Cytotoxicity analysis of the deep-penetrating iron-death nano-formulation in Experimental Example 1 of this invention;

[0031] Figure 7 This is the result of macrophage polarization regulated by the deep-penetrating iron-death nanoparticle formulation in Experiment Example 2 of this invention;

[0032] Figure 8 This is the result of TGF-β secretion regulated by deep-penetrating iron-death nanoparticles in Experiment Example 2 of this invention;

[0033] Figure 9 This is the result of deep-penetrating iron-death nano-formulation regulating fiber blast activation in Experimental Example 3 of the present invention;

[0034] Figure 10 This illustrates the deep penetration effect of the deep-penetrating iron-death nanoparticles in in vitro multicellular tumor spheres in Experimental Example 4 of this invention.

[0035] Figure 11 This is the in vivo efficacy evaluation result of the deep-penetrating iron-death nano-formulation in Experimental Example 5 of the present invention. Detailed Implementation

[0036] To make the technical problems, technical solutions and advantages of the present invention clearer, a detailed description will be given below in conjunction with the accompanying drawings and specific embodiments.

[0037] The following embodiments are used to illustrate the present invention, but are not intended to limit the scope of the invention. Any modifications or substitutions made to the methods, steps, or conditions of the present invention without departing from the spirit and essence of the invention are within the scope of the invention.

[0038] Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art; unless otherwise specified, the reagents used in the embodiments are all commercially available.

[0039] Example 1

[0040] Preparation of deep-penetrating iron-death nanoparticles (PTFE)

[0041] An appropriate amount of tannic acid was dissolved in 5 mL of ultrapure water to obtain a concentration of 160 μg / mL, which was used as the aqueous phase. Appropriate amounts of PLGA, FeCl3, and Erastin were dissolved in 1 mL of acetone to obtain the organic phase, with concentrations of 2 mg / mL PLGA, 0.4 mg / mL FeCl3, and 0.24 mg / mL Erastin, respectively. The organic phase was slowly added dropwise to the aqueous phase under ultrasonic conditions, followed by stirring at a constant temperature of 37°C in a water bath for 3 hours to allow complete evaporation of the organic solvents. The resulting solution was centrifuged, washed with ultrapure water, and reconstituted to obtain the nano-formulation PTFE.

[0042] Based on the nanoformulation obtained in Example 1, the physicochemical properties and pharmaceutical characteristics of the deep-penetrating iron death nanoformulation were tested, specifically including micromorphology, particle size, stability, acid sensitivity, Fenton effect, cytotoxicity, deep penetration ability, and in vivo efficacy evaluation, with the relevant nanoformulation obtained in Example 1 being specifically described.

[0043] Experimental Example 1

[0044] (1) Examining the morphology of nano-formulations under transmission electron microscopy

[0045] Take the nano-formulation prepared in Example 1, drop it onto a 300-mesh copper grid covered with a carbon film, place it in a constant temperature drying oven, and observe it under a transmission electron microscope after it dries.

[0046] The results are as follows Figure 1 As shown: The deep-penetrating iron death nanoparticles prepared by this invention have a uniform particle size distribution, are nearly spherical, have a distinct core-shell structure, a particle size of about 70 nm, and a shell thickness of about 10 nm.

[0047] (2) Analysis of elements in nano-formulations

[0048] The nano-formulation prepared in Example 1 was dropped onto a 300-mesh copper grid covered with a carbon film and placed in a constant temperature drying oven. After drying, it was placed in a transmission electron microscope-energy dispersive X-ray scattering spectrometer (TEMEDS) to analyze the elemental composition of the nano-formulation.

[0049] The results are as follows Figure 2 As shown, the elemental analysis of the nano-formulation prepared by this invention contains C, N, O, Fe, and Cl, among which Cl is a unique element of Erastin, proving that the nano-formulation was successfully loaded with Erastin and iron ions.

[0050] (3) Investigate the stability of nano-formulations

[0051] The nanoparticles prepared in Example 1 were added to equal amounts of water, PBS (10 mM, pH 7.4), and DMEM (10% FBS) to investigate the changes in nanoparticle size and PDI over time.

[0052] The results are as follows Figure 3 As shown, the nanoparticles exhibit good stability in water, PBS, and DMEM.

[0053] (4) Investigate the acid sensitivity of nano-formulations

[0054] The nano-formulation prepared in Example 1 was centrifuged and dispersed in MES (10 mM, pH 5.5) and PBS (10 mM, pH 7.4) solutions, respectively, and incubated at 37°C. The supernatant was collected by centrifugation at 0 h, 0.5 h, 1 h, 2 h, 4 h, 8 h, and 12 h. Erastin release was detected by high performance liquid chromatography. Simultaneously, the precipitate was spotted onto a 300-mesh copper grid covered with a carbon film and placed in a constant temperature drying oven. After drying, it was observed under a transmission electron microscope.

[0055] from Figure 4 From A, we know that at pH 5.5, 80% is released in 0.5 hours; however, at pH 7.4, Erastin releases less than 30% after 24 hours. Figure 4 B, Figure 4 As shown in Figure C, the nano-formulation gradually disintegrates at pH 5.5, exhibiting incomplete morphology and a significant disappearance of the core-shell structure. However, at pH 7.4, the nano-formulation maintains its core-shell structure, with intact nanoparticle morphology and uniform particle size. Based on the above images, it can be concluded that this nano-formulation is acid-sensitive, disintegrating only within the tumor microenvironment to exert its therapeutic effect.

[0056] (5) Investigating the Fenton effect of nano-formulations

[0057] Iron ions react with hydrogen peroxide (H2O2) within tumor cells to generate highly reactive hydroxyl radicals (·OH), which can trigger cellular lipid peroxidation. Methylene blue can be degraded by ·OH, changing it from blue to colorless. The nano-formulation prepared in Example 1 was used as a control, and methylene blue (MB) and H2O2 were added. The experimental phenomena were observed, and 100 μL of the reaction solution was transferred to an ELISA plate. The absorption spectrum was scanned in the wavelength range of 400–800 nm using an ELISA reader.

[0058] The results are as follows Figure 5 As shown in the figure, iron ions can decolorize MB, and the characteristic absorption peak at 600-700 nm disappears. This nano-formulation can also decolorize MB, and the reaction process is efficient and rapid, indicating that this nano-formulation can initiate an efficient Fenton reaction to generate hydroxyl radicals.

[0059] (6) Investigate the cytotoxicity of nano-formulations

[0060] KPC1199 pancreatic cancer cells in logarithmic growth phase were treated with 5 × 10⁻⁶ cells. 3 Cells were seeded at a density of [number] cells / well in 96-well plates and incubated statically in a cell culture incubator. After attachment, the culture medium was discarded, and 100 μL of pre-prepared culture medium containing different concentrations of nanoparticles was added. The plates were then incubated statically for 24 h. After incubation, the culture medium was carefully aspirated, and the cells were washed twice with PBS. 100 μL of 0.5 mg / mL MTT solution was added to each well. Cell viability was determined using the MTT assay.

[0061] The results are as follows Figure 6 As shown, the IC50 of this nano-formulation is 7.62 μM, indicating that the nano-formulation can disrupt the redox homeostasis of the tumor site and induce ferroptosis in pancreatic cancer cells.

[0062] Experiment Example 2

[0063] Investigating the regulation of macrophage polarization and TGF-β secretion by nano-formulation

[0064] RAW264.7 cells in logarithmic growth phase were injected with 1×10⁻⁶ cells. 5 RAW264.7 cells were seeded at a density of 1 cells / well in 12-well plates. After adhesion, the culture medium was carefully discarded, and the cells were washed twice with PBS. Fresh complete culture medium containing IL-4 (100 ng / mL) was added, and the plates were incubated for 24 h to stimulate the formation of M2 macrophages, mimicking tumor-associated macrophages in the tumor microenvironment. The supernatant was discarded, and culture medium containing nanoparticles was added. Flow cytometry was used to detect CD206 expression on the cell surface, and ELISA was used to detect TGF-β secretion.

[0065] The results are as follows Figure 7 As shown in Figure 8, Figure 7 The results of macrophage polarization regulated by deep-penetrating ferrode nanoparticles were shown. The relative fluorescence intensity indicated the relative number of macrophages. Under IL-4 stimulation, the number of M2 macrophages increased. After the addition of the nanoparticles of the present invention to M2 macrophages, the number of M2 macrophages decreased significantly, indicating that macrophages polarized from M2 to M1 under the influence of the nanoparticles. Figure 8 The results of TGF-β secretion after macrophage polarization were obtained by deep-penetrating ferroptosis nanoparticle formulation. TGF-β is mainly expressed by M2 macrophages. Under IL-4 stimulation, macrophages are induced to become M2 macrophages. After the addition of the nanoparticle formulation of the present invention, TGF-β was significantly reduced, indicating that the TGF-β expressed by macrophages will be reduced under the influence of the nanoparticle formulation.

[0066] In summary, this nano-formulation can regulate macrophage polarization from M2 to M1 and reduce macrophage TGF-β secretion.

[0067] Experimental Example 3

[0068] Investigating the effect of nano-formulations on fibroblast activation

[0069] M2 macrophages were constructed at a ratio of 1×10⁻⁶. 5 Inoculate 12-well plates at a density of 10 cells / well. After the cells adhere to the walls, carefully discard the culture medium and add Erastin and Fe2+ to each well. 3+ Complete culture medium was used for PTFE NPs, while the control group received complete culture medium without nanoparticles. After 24 hours of incubation, the supernatant from each group was transferred to unactivated fibroblasts at a cell density of 1×10⁻⁶ cells / cells. 5 Cells were incubated per well for 24 hours. After incubation, cells were digested, the supernatant was discarded, and BD fixation / permeabilization working solution was added. Cells were incubated at 4°C in the dark for 20 minutes. Cells were washed twice with BD washing buffer, and Anti-α-SMA antibody was added. Cells were incubated at 4°C in the dark for 20 minutes. Excess unbound antibody was washed away, and fluorescently labeled secondary antibody was added. Cells were incubated at 4°C in the dark for 20 minutes. Excess unbound antibody was washed away, and finally, cells were resuspended in 0.5 mL PBS. Flow cytometry was used for analysis, and fluorescence intensity was semi-quantitatively measured.

[0070] The results are as follows Figure 9As shown, α-SMA is an important marker of fibroblast activation, and its increased expression indicates fibroblast activation, further exacerbating the formation of the dense tumor microenvironment. In the control group, fibroblasts stimulated with M2 macrophage supernatant showed the highest α-SMA expression. Compared to the control group, the fluorescence intensity of α-SMA hardly changed after adding Erastin alone, indicating that Erastin alone cannot inhibit fibroblast activation. However, the addition of iron ions alone significantly reduced fibroblast activation, and the nano-formulation prepared in this invention was more effective in reducing fibroblast activation than iron ions alone. This suggests that Erastin and Fe in the nano-formulation prepared in this method... 3+ It has a synergistic therapeutic effect, enhancing the effects of Erastin alone or iron alone.

[0071] In summary, this nano-formulation mainly reduces fibroblast activation through the synergistic effect of iron ions and Erastin, thereby regulating the dense tumor microenvironment and making it more conducive to deep penetration.

[0072] Experiment Example 4

[0073] Investigating the deep penetration effect of nano-formulations

[0074] Weigh 0.15 g of agarose and dissolve it in 10 mL of PBS (10 mM, pH 7.4) to prepare a 1.5% agarose solution. After autoclaving, pipette 80 μL of the solution into a 96-well plate while still hot, let it stand for 30 min, and then inoculate cells after the agarose has cooled and solidified. Inoculate logarithmically growing KPC1199 cells at a rate of 1 × 10⁻⁶ cells / well. 4 KPC1199 cells were seeded at a density of cells / well in 96-well plates containing agarose and placed in a cell culture incubator. After 48 hours of culture, tumor spheres were formed.

[0075] Add the cell proliferation tracking fluorescent probe CFDA-SE (working concentration 10 μM) to the NIH3T3 cell suspension and incubate in the dark for 15 min to complete staining. Then, transfer the pre-stained NIH3T3 cells to a container at a concentration of 1 × 10⁻⁶ cells / mL. 4 KPC1199 cells were seeded at a density of cells / well in 96-well plates containing agarose. The cultured KPC1199 tumor spheres were carefully aspirated and transferred to 96-well plates containing pre-stained NIH3T3 cells. The plates were then placed in a cell culture incubator and cultured for 48 hours to form KPC1199@NIH3T3 bilayer tumor spheres.

[0076] Carefully aspirate the culture from the bilayer tumor spheres and add complete culture medium containing PTFE@Cy5.5. After incubation for 24 hours, carefully aspirate the tumor spheres, wash twice with pre-cooled PBS, fix with 4% paraformaldehyde for 10 minutes, and observe the drug penetration of the tumor spheres using a fluorescence confocal microscope.

[0077] The results are as follows Figure 10 As shown in the figure, the PTFE@Cy5.5 treated group has many fluorescently labeled nanoparticles in the middle of the bilayer tumor spheres, indicating that the preparation has a deep penetration effect.

[0078] Experimental Example 5

[0079] Investigating the in vivo efficacy of nano-formulations

[0080] Animal model construction: Logarithmic growth phase pancreatic cancer cells (KPC1199) and fibroblasts (NIH3T3) were digested with trypsin, and the cell suspension was diluted to adjust cell density. The hair near the right axilla of mice was shaved, and 100 μL of the two cell types were mixed and subcutaneously injected, resulting in an inoculation density of 6.6 × 10⁶ cells per mouse for KPC1199. 5 Individuals / pieces, NIH3T3: 3.3 × 10 5 Each mouse was observed regularly for its condition and the formation of subcutaneous tumors.

[0081] The tumor has grown to approximately 100 mm in size. 3 Mice were randomly divided into 4 groups (PBS group, Fe ... 3+ Five animals were included in each of the three groups: the Erastin group, the PTFE group, and the Fe group. The drugs were administered via tail vein injection at a dose of Erastin 5 mg / kg. 3+ 7.3 mg / kg, administered every three days. H&E staining of tumor tissue was performed.

[0082] The results are as follows Figure 11 As shown, compared with the other three groups, the PTFE-treated group exhibited the most significant nuclear necrosis and cavitation in the H&E-stained sections of the tumor, indicating that Fe... 3+ Synergistic effect with Erastin.

[0083] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations here. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A deep-penetrating ferrodeation nanoparticle formulation for pancreatic cancer, characterized in that, The nanoformulation comprises a drug-loaded core and a MOF shell. The drug-loaded core is polymerized from the ferroptosis inducer Erastin and a polymer material. The MOF shell is formed by coordination of iron ions and tannic acid. The polymer material is polylactic acid-glycolic acid copolymer. The preparation method of the deep-penetrating ferrodeation nanoparticle formulation for pancreatic cancer includes the following steps: S1. Dissolve tannic acid in water and use it as the aqueous phase for later use; S2. Add the polymer material, iron ions, and Erastin to an organic reagent and dissolve them to form the organic phase; S3. Under ultrasonic conditions, the organic phase liquid is slowly dripped into the aqueous phase, and then stirred under constant temperature conditions in a water bath to allow the organic solvent to evaporate completely. The resulting solution is centrifuged, washed with ultrapure water, and reconstituted to obtain a deep-penetrating iron death nano-formulation for pancreatic cancer.

2. The pancreatic cancer deep-penetrating ferrodeation nano-formulation according to claim 1, characterized in that, The molar ratio of tannic acid to iron ions is 1:10 to 10:

1.

3. The pancreatic cancer deep-penetrating ferrodeation nano-formulation according to claim 1, characterized in that, The nano-formulation has a regular spherical core-shell structure with a particle size of about 70 nm and a shell thickness of about 10 nm.

4. A method for preparing a deep-penetrating iron-death nanoparticle formulation for pancreatic cancer as described in any one of claims 1 to 3, characterized in that, Includes the following steps: S1. Dissolve tannic acid in water and use it as the aqueous phase for later use; S2. Add the polymer material, iron ions, and Erastin to an organic reagent and dissolve them to form the organic phase; S3. Under ultrasonic conditions, the organic phase liquid is slowly dripped into the aqueous phase, and then stirred under constant temperature conditions in a water bath to allow the organic solvent to evaporate completely. The resulting solution is centrifuged, washed with ultrapure water, and reconstituted to obtain a deep-penetrating iron death nano-formulation for pancreatic cancer.

5. The preparation method according to claim 4, characterized in that, In step S2, the concentration ratio of polymer material, iron ions and Erastin is 25:5:

3.

6. The preparation method according to claim 4, characterized in that, The organic reagent in step S2 is either acetone or acetonitrile.

7. The preparation method according to claim 4, characterized in that, In step S3, the water bath temperature is maintained at 20~40℃, and the stirring time is 1~6 h.

8. The use of a pancreatic cancer deep-penetrating ferrode nanoformulation as described in any one of claims 1 to 3, or a pancreatic cancer deep-penetrating ferrode nanoformulation prepared by the preparation method as described in any one of claims 4 to 7, in the preparation of anti-pancreatic cancer drugs.

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