Drug delivery system of targeted neutrophil extracellular trap net and preparation method and application thereof
By constructing Fe3O4@mPDA nanocarriers and combining magnetic targeting and photothermal therapy, targeted delivery of the chemotherapy drugs DOX and DNase I was achieved, solving the problem of the lack of multifunctional nano-formulations in existing technologies and realizing the synergistic effect of tumor treatment and metastasis prevention.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- XINXIANG MEDICAL UNIV
- Filing Date
- 2026-01-26
- Publication Date
- 2026-05-12
AI Technical Summary
Existing technologies lack a targeted drug delivery system that can integrate multiple mechanisms to synergistically exert anti-tumor and anti-metastasis effects, especially a multifunctional nanoformulation that combines chemotherapy drugs, NETs degradation, and CCDC25-mediated active targeting functions, and possesses magnetic response and photothermal therapy capabilities.
Using superparamagnetic iron oxide nanoparticles as the core, a mesoporous polydopamine shell nanocarrier Fe3O4@mPDA is constructed, which is co-loaded with the chemotherapy drugs DOX and DNase I. The surface is modified with CCDC25 targeting molecules to achieve specific recognition and drug release in the tumor microenvironment. Combined with magnetic targeting and photothermal therapy, it synergistically enhances the efficacy of chemotherapy and photothermal therapy.
It significantly improves the accumulation of drug molecules at the lesion site, enhances local drug concentration, prolongs the in vivo half-life of DNase I, disrupts the DNA backbone of NETs, inhibits tumor growth and metastasis, and achieves synergistic effects of chemotherapy and photothermal therapy.
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Figure CN122005490A_ABST
Abstract
Description
Technical Field
[0002] This invention belongs to the field of targeted drug delivery system technology, specifically relating to a drug delivery system that targets extracellular traps of neutrophils, its preparation method, and its application. Background Technology
[0004] Neutrophils are important innate immune cells that capture and clear pathogens during the fight against invasion by releasing extracellular neutrophil traps (NETs). NETs are a network structure composed of DNA, histones, and various antimicrobial proteins; however, they are released excessively and dysregulated under pathological conditions such as tumors, exhibiting significant pro-tumor effects. Studies have shown that cytokines and growth factors carried by NETs can remodel the tumor microenvironment, promoting tumor cell invasion and distant metastasis. Therefore, targeting and regulating the formation and clearance of NETs is considered a potential strategy for inhibiting tumor proliferation and preventing metastasis.
[0005] Currently, strategies for regulating NETs mainly include inhibiting their formation and directly degrading existing NETs. On the one hand, the release of NETs can be reduced at the source by inhibiting the activity of key proteins such as peptidylarginine deiminase 4 and neutrophil elastase, or by intervening in related signaling pathways such as MAPK and cGAS-STING. On the other hand, directly degrading existing NETs, especially by disrupting their DNA backbone, is a direct and effective method. DNase I, as a non-specific endonuclease, can digest single-stranded or double-stranded DNA and has been shown to significantly attenuate NET-mediated tumor growth and metastasis. However, DNase I has a short half-life in vivo and is easily inactivated, limiting its clinical application. To improve its stability and targeting, researchers have attempted to load DNase I onto nanocarriers or combine it with targeting peptides to achieve efficient and precise degradation of NETs.
[0006] Recent studies have further revealed the molecular mechanisms by which NETs promote tumor metastasis. For example, the transmembrane protein CCDC25 on the surface of cancer cells has been shown to act as a specific receptor for NETs-DNA. After binding, it can activate downstream signaling pathways such as ILK-β-parvin, inducing cytoskeleton remodeling and enhancing the migration, adhesion, and proliferation of tumor cells. Therefore, blocking the interaction between CCDC25 and NETs-DNA or utilizing CCDC25-mediated targeted drug delivery systems to specifically clear NETs has become a research hotspot for inhibiting tumor metastasis.
[0007] While existing technologies have addressed NET inhibition, degradation, and CCDC25 targeting strategies, a systematic delivery platform capable of integrating multiple mechanisms to synergistically exert anti-tumor and anti-metastatic effects remains lacking. In particular, multifunctional nanoparticles combining chemotherapeutic drugs, NET degradation, and CCDC25-mediated active targeting, while simultaneously endowing the system with magnetic responsiveness and photothermal therapy capabilities, have not yet been reported. Therefore, developing a composite nanomedicine delivery system capable of efficient loading, targeted delivery, and controlled release within the tumor microenvironment is of great significance for achieving synergistic effects in tumor treatment and metastasis control. Summary of the Invention
[0009] The purpose of this invention is to provide a composite nanomedicine delivery system with active targeting function and synergistic inhibition of tumor growth and metastasis, and its preparation method. This composite nanomedicine system integrates multiple mechanisms such as magnetic targeting, photothermal therapy, chemotherapy and NETs degradation through a multifunctional integrated design, aiming to improve anti-tumor efficacy and reduce systemic toxic side effects.
[0010] To achieve the above objectives, this invention employs the following technical solution: a drug delivery system targeting neutrophil extracellular traps. This system utilizes superparamagnetic iron oxide nanoparticles as the core, with a mesoporous polydopamine shell constructed on their surface to form a core-shell structure, Fe3O4@mPDA nanocarrier. This Fe3O4@mPDA nanocarrier efficiently co-loads the chemotherapeutic drug DOX and DNase I, which degrades neutrophil extracellular traps, into drug-loaded nanoparticles. The surface modification of these drug-loaded nanoparticles specifically recognizes and binds to CCDC25, the targeting molecule of neutrophil extracellular traps, thereby constructing a drug delivery system targeting neutrophil extracellular traps. This drug delivery system targets neutrophil extracellular traps in the tumor microenvironment and promotes drug molecule release under photothermal action, achieving synergistic effects of chemotherapy and photothermal therapy at the tumor site. Simultaneously, it degrades overexpressed neutrophil extracellular traps in the tumor microenvironment, thereby disrupting the pre-metastatic tumor microenvironment.
[0011] The innovation of this invention lies in the following: In vivo active targeted delivery is achieved through the specific recognition of NETs in the tumor microenvironment by CCDC25, significantly improving the accumulation of drug molecules at the lesion site; the superparamagnetism of the iron oxide core enables physical magnetic targeting and retention of drug molecules under the guidance of an external magnetic field, further enhancing local drug concentration; the mesoporous polydopamine shell not only provides a high-capacity carrier for drug molecule loading and prolongs the in vivo half-life of DNase I, but also endows it with excellent photothermal conversion properties; the photothermal effect generated by the drug delivery system under near-infrared light irradiation can both kill tumor cells and trigger the controlled release of drug molecules, achieving synergistic effects of chemotherapy and photothermal therapy; the DNase I released controllably after targeted delivery can effectively degrade the DNA backbone of NETs, disrupting their tumor-promoting microenvironment, thereby inhibiting the growth of primary tumors while preventing distant metastasis. The preparation method described in this invention is process-controllable, and the prepared delivery system has multiple targeting, synergistic therapy, and microenvironment regulation functions, providing a new strategy and means for the prevention and treatment of tumors and their metastases.
[0012] The preparation method of the drug delivery system targeting neutrophil extracellular traps described in this invention includes the following specific preparation steps:
[0013] Step S1: Preparation of superparamagnetic iron oxide nanoparticles
[0014] Ferric chloride hexahydrate, sodium acetate and sodium citrate dihydrate were dispersed in ethylene glycol and stirred until homogeneous. The mixture was then reacted in a reactor at 180-220°C. After the reaction was completed, the product was washed with ethanol and distilled water respectively and then magnetically separated to obtain superparamagnetic iron oxide nanoparticles.
[0015] Step S2: Preparation of Fe3O4@mPDA nanocarrier
[0016] Prönnik F127 and 1,3,5-trimethylbenzene were added to a mixed solution of deionized water and ethanol and stirred thoroughly until emulsified. Then, tris(hydroxymethyl)aminomethane, dopamine and the superparamagnetic iron oxide nanoparticles obtained in step S1 were added in sequence and reacted at room temperature. After the reaction was completed, the product was magnetically separated and the precipitate was washed with a mixture of anhydrous ethanol and acetone to obtain the core-shell structured nanocarrier Fe3O4@mPDA.
[0017] Step S3: Preparation of drug-loaded nanoparticles Fe3O4@mPDA-DOX-DNase I
[0018] The Fe3O4@mPDA nanocarrier obtained in step S2 was dispersed in deionized water, and then an aqueous solution of DOX was added. The reaction was carried out at 2-6°C with stirring in the dark. After the reaction was completed, the product was separated by centrifugation to obtain drug-loaded nanoparticles Fe3O4@mPDA-DOX. The drug-loaded nanoparticles Fe3O4@mPDA-DOX were dispersed in deionized water and an aqueous solution of DNase I was added. The reaction was carried out under ice bath conditions with stirring in the dark. After the reaction was completed, the product was magnetically separated to obtain drug-loaded nanoparticles Fe3O4@mPDA-DOX-DNase I.
[0019] Step S4: Modification of drug-loaded nanoparticles by membrane protein CCDC25
[0020] Viral fluid containing CCDC25 was co-incubated with 4T1 cells. After 24 hours of transfection, positive transfected cells were selected and CCDC25-overexpressing 4T1 cells were obtained and labeled as C-4T1 cells. C-4T1 cells were expanded, and extraction reagent A containing a cocktail protease inhibitor was added. After incubation, repeated freeze-thaw cycles were performed to lyse the cells. Cell membrane fragments containing CCDC25 were collected by centrifugation, and membrane protein extraction reagent B was added to fully extract CCDC25 protein. The supernatant of membrane protein CCDC25 was collected by high-speed centrifugation. Membrane protein CCDC25 and drug-loaded nanoparticles Fe3O4@mPDA-DOX-DNase Ⅰ were placed in a liposome extractor, and the product was then separated by magnetic separation to obtain CCDC25-modified drug-loaded nanoparticles, which are drug delivery systems targeting the extracellular trap of neutrophils, and labeled as CCDC25-Fe3O4@mPDA-DOX-DNase Ⅰ.
[0021] Furthermore, the specific process of modifying the drug-loaded nanoparticles with the membrane protein CCDC25 in step S4 is as follows: the membrane protein CCDC25 and the drug-loaded nanoparticle Fe3O4@mPDA-DOX-DNase Ⅰ are taken at a mass ratio of 1:1000 and protein solutions and drug-loaded nanoparticle aqueous solutions are prepared respectively. The protein solutions and drug-loaded nanoparticle aqueous solutions are placed on both sides of the liposome extruder and extruded 8 to 12 times. Then, magnetic separation is performed to obtain the drug delivery system CCDC25-Fe3O4@mPDA-DOX-DNase Ⅰ.
[0022] The application of the drug delivery system targeting neutrophil extracellular traps described in this invention in the preparation of drugs for treating and / or preventing tumors and tumor metastasis, wherein the drugs exert their effects through the following mechanisms: ferric oxide is magnetically detained at the lesion site, increasing local drug concentration; the targeting molecule CCDC25 guides the drug delivery system to specifically accumulate in the neutrophil extracellular trap region of the tumor microenvironment; DNase I degrades the DNA backbone of the neutrophil extracellular traps, disrupting the metastatic microenvironment; the chemotherapeutic drug DOX kills tumor cells; and the mesoporous polydopamine shell generates a photothermal effect under near-infrared light irradiation, killing tumor cells.
[0023] The application of the drug delivery system targeting neutrophil extracellular traps described in this invention in the preparation of chemotherapy-photothermal therapy synergistic tumor drugs.
[0024] Compared with the prior art, the present invention has the following advantages and superior effects: The multifunctional integrated design prepared by the present invention combines in vitro magnetic targeting with in vivo specific recognition. The core-shell structure Fe3O4@mPDA is both a drug carrier and a therapeutic agent, realizing the synergistic effect of tumor chemotherapy and photothermal therapy, and destroying the microenvironment of tumor metastasis. It has good application prospects in tumor treatment and prevention of tumor metastasis. Attached Figure Description
[0026] Figure 1 To construct magnetic nanoparticles targeting NETs and their application in tumor therapy and the degradation of NETs in the tumor microenvironment.
[0027] Figure 2 Scanning electron microscope (SEM) images, transmission electron microscope (TEM) images, and hydrodynamic diameter and particle size distribution of Fe3O4 nanoparticles (A, B, C) and Fe3O4@mPDA nanocarriers (D, E, F).
[0028] Figure 3 The images show the heating curve of Fe3O4@mPDA nanocarrier under 808nm laser light (A), the photothermal stability image of 100μg / mL Fe3O4@mPDA nanocarrier (B), and the thermal imaging image of ultrapure water and Fe3O4@mPDA nanocarrier (100μg / mL) (C).
[0029] Figure 4 Fluorescence image of C-4T1 cells (A), CCDC25 plasmid map (B), and Western blot image of membrane protein CCDC25 (C).
[0030] Figure 5Agarose gel electrophoresis of DNA reacted with free DNase-1, Fe3O4@mPDA, Fe3O4@mPDA-DOX-DNase Ⅰ, and CCDC25-Fe3O4@mPDA-DOX-DNase Ⅰ.
[0031] Figure 6 Images of Sitox Green-stained NETs (A), 4T1 cells and C-4T1 cells after co-incubation with NETs (B), and quantitative fluorescence analysis of the migrating cells using ImageJ (C). Detailed Implementation
[0033] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments, but this should not be construed as limiting the invention. Unless otherwise specified, the technical means used in the following embodiments are conventional means well known to those skilled in the art, and the materials, reagents, etc. used in the following embodiments are commercially available unless otherwise specified.
[0034] Example 1
[0035] Preparation of superparamagnetic iron oxide nanoparticles:
[0036] 540 mg of ferric chloride hexahydrate was added to 20 mL of ethylene glycol and stirred until dissolved. Then, 1.03 mg of sodium acetate and 294.1 mg of sodium citrate dihydrate were added and magnetically stirred for 30 min. The mixture was then transferred to a high-pressure reactor and reacted at 200 °C for 8 h. After the reaction was completed, the product was washed with ethanol and distilled water, and then magnetically separated to obtain the superparamagnetic iron oxide nanoparticles.
[0037] Preparation of Fe3O4@mPDA nanocarriers:
[0038] A mixture of 40 mL distilled water and 20 mL ethanol was prepared. 400 mg of Prönkel F127 and 750 μL of 1,3,5-trimethylbenzene were added to the mixture of ethanol and water and magnetically stirred for 30 min until completely emulsified. Then, 65 mg of tris(hydroxymethyl)aminomethane, 60 mg of dopamine and 20 mg of iron(III) oxide nanoparticles were added sequentially. The mixture was mechanically stirred (400 rpm) and stirred evenly. The mixture was then reacted at room temperature for 24 h. After the reaction was completed, the precipitate was washed three times with a mixture of anhydrous ethanol and acetone (V / V=5:2) and then magnetically separated to obtain Fe3O4@mPDA nanocarrier.
[0039] Loading of drug molecules on Fe3O4@mPDA nanocarriers:
[0040] 4 mg of Fe3O4@mPDA nanocarrier was dispersed in 2 mL of water, and 1 mg of DOX·HCl was dispersed in 1 mL of water. The two solutions were mixed thoroughly and magnetically stirred overnight at 4°C in the dark. DOX was loaded onto the Fe3O4@mPDA nanocarrier via physical adsorption. The Fe3O4@mPDA-DOX drug-loaded nanoparticles were then obtained by centrifugation. 1 mg of DNase I was dissolved in 1 mL of water and added to 3 mL of the above Fe3O4@mPDA-DOX drug-loaded nanoparticle solution. The mixture was stirred in an ice bath in the dark for 24 h, and then magnetically separated to obtain Fe3O4@mPDA-DOX-DNase I drug-loaded nanoparticles. The DOX content was determined using a UV spectrophotometer at 482 nm, and the DNase I content was determined using the BCA protein assay at a full-wavelength microplate reader at 562 nm.
[0041] Modification of drug-loaded nanoparticles by membrane protein CCDC25:
[0042] 4T1 cells were used at 16 × 10⁴ cells per well. 4Cells were seeded at a density of [number] cells / well in 12-well plates and cultured overnight in complete medium until complete adherence. Frozen CCDC25 virus solution (purchased from Yunzhou Biotechnology (Guangzhou) Co., Ltd.) was thawed in an ice bath. After discarding the original medium in the plates, 200 μL of a mixed culture medium prepared by mixing 25 μL of CCDC25 virus solution and 175 μL of fresh medium (RPMI-1640 medium, Beijing Solarbio Science & Technology Co., Ltd.) was added to each well. Polybrene was then added to the mixed culture medium to a final concentration of 8 μg / mL. Viral infection was carried out overnight at 37°C and 5% CO2, with cell morphology observed periodically. 24 h after transfection, the virus-containing medium was removed and replaced with complete medium (RPMI-1640 medium and fetal bovine serum at a volume ratio of 9:1, fetal bovine serum from Bioind, Israel) for continued culture. To screen successfully transfected cells, a puromycin selection medium (a complete medium containing 2 μg / mL puromycin, i.e., a complete medium prepared by mixing RPMI-1640 medium containing 2 μg / mL puromycin with fetal bovine serum at a volume ratio of 9:1) was prepared and the cells were screened continuously for 72 hours. The puromycin-resistant cells obtained were the 4T1 cell line stably overexpressing CCDC25, and were labeled as C-4T1 cells. C-4T1 cells were expanded to approximately 20-50 million. The cell pellet was resuspended in ice-cold PBS, centrifuged, and then collected. Extraction reagent A (1.5 mL of Opti-MEM® I medium (purchased from Invitrogen) and 5 μg of DNA (containing packaging plasmids pMD2.G, pMDL / gpRRE, pRSV-Rev, and the target gene plasmid in a 1:1:1:2 ratio, purchased from Yunzhou Biotechnology (Guangzhou) Co., Ltd.) containing a cocktail protease inhibitor (Sigma-Aldrich, USA) was gently resuspended and incubated on ice for 10-15 min. Cells were then lysed using a liquid nitrogen freeze-thaw cycle, and the lysed cells were purified by centrifugation. Add 200 μL of membrane protein extraction reagent B (extraction reagent B is 1.5 mL of Opti-MEM® I culture medium and 40 μL of Lipofectamine 2000 (Lipofectamine 2000 was purchased from Invitrogen), and extract reagent B was purchased from Yunzhou Biotechnology (Guangzhou) Co., Ltd.) to the C-4T1 cell debris to resuspend the precipitate. Incubate on ice for 5-10 min, centrifuge multiple times, and collect the supernatant containing membrane protein CCDC25.Membrane protein CCDC25 and Fe3O4@mPDA-DOX-DNaseⅠ drug-loaded nanoparticles were taken at a mass ratio of 1:1000. The drug-loaded nanoparticle aqueous solution and the protein solution were placed on both sides of a liposome extruder and extruded 10 times. Then, the drug-loaded nanoparticles modified with membrane protein CCDC25 were obtained by magnetic separation and labeled as CCDC25-Fe3O4@mPDA-DOX-DNaseⅠ.
[0043] The foregoing has shown and described the basic principles, main features and advantages of the present invention. Various changes and modifications can be made to the present invention without departing from the spirit and scope thereof, and all such changes and modifications fall within the scope of the present invention as claimed.
Claims
1. A drug delivery system targeting neutrophil extracellular traps, characterized in that: The drug delivery system employs superparamagnetic iron oxide (Fe3O4) nanoparticles as the core, with a mesoporous polydopamine (mPDA) shell constructed on its surface, forming a core-shell structured nanocarrier Fe3O4@mPDA. This Fe3O4@mPDA nanocarrier utilizes its mesoporous structure to efficiently co-load the chemotherapeutic drug doxorubicin (DOX) and deoxyribonuclease I (DNase I), which degrades the extracellular trap of neutrophils, resulting in drug-loaded nanoparticles. The surface modification of these drug-loaded nanoparticles enables them to specifically recognize and bind to coiled-coil domain protein 25 (CCDC25), the targeting molecule of the extracellular trap of neutrophils, thereby constructing a drug delivery system targeting the extracellular trap of neutrophils. This drug delivery system targets the extracellular trap of neutrophils in the tumor microenvironment and promotes the release of drug molecules under photothermal action, achieving synergistic effects of chemotherapy and photothermal therapy at the tumor site. Simultaneously, it degrades the overexpressed extracellular trap of neutrophils in the tumor microenvironment, thereby disrupting the pre-metastatic tumor microenvironment.
2. The drug delivery system targeting neutrophil extracellular traps according to claim 1, characterized in that: The drug delivery system is surface-modified with CCDC25, which specifically recognizes and binds to the deoxyribonucleic acid (DNA) components in the neutrophil extracellular trap, thereby enabling the drug delivery system to actively target the tumor microenvironment region enriched by the neutrophil extracellular trap. Ferric oxide (Fe3O4) endows the drug delivery system with magnetic responsiveness, allowing it to remain at the lesion site under an external magnetic field, increasing local drug concentration. The mesoporous polydopamine shell possesses near-infrared photothermal conversion properties, generating a photothermal effect under near-infrared light irradiation, thus synergistically enhancing the anti-tumor effect with the chemotherapy of DOX. DNase I is protected in the Fe3O4@mPDA nanocarrier, resulting in improved in vivo stability and half-life, thereby enhancing the degradation efficiency of the neutrophil extracellular trap DNA backbone and disrupting the pre-metastatic tumor microenvironment. Through the synergistic effect of multiple mechanisms—chemotherapy, photothermal therapy, and targeted degradation of the neutrophil extracellular trap—the drug delivery system can simultaneously inhibit the growth of the primary tumor and prevent tumor metastasis.
3. A method for preparing a drug delivery system targeting an extracellular trapping net of neutrophils as described in claim 1 or 2, characterized in that... The specific preparation steps are as follows: Step S1: Preparation of superparamagnetic iron oxide nanoparticles Ferric chloride hexahydrate, sodium acetate and sodium citrate dihydrate were dispersed in ethylene glycol and stirred until homogeneous. The mixture was then reacted in a reactor at 180-220°C. After the reaction was completed, the product was washed with ethanol and distilled water respectively and then magnetically separated to obtain superparamagnetic iron oxide nanoparticles. Step S2: Preparation of Fe3O4@mPDA nanocarrier Prönnik F127 and 1,3,5-trimethylbenzene were added to a mixed solution of deionized water and ethanol and stirred thoroughly until emulsified. Then, tris(hydroxymethyl)aminomethane, dopamine (PODA) and superparamagnetic iron oxide nanoparticles obtained in step S1 were added in sequence and reacted at room temperature. After the reaction was completed, the product was magnetically separated and the precipitate was washed with a mixture of anhydrous ethanol and acetone to obtain the core-shell structured nanocarrier Fe3O4@mPDA. Step S3: Preparation of drug-loaded nanoparticles Fe3O4@mPDA-DOX-DNase I The Fe3O4@mPDA nanocarrier obtained in step S2 was dispersed in deionized water, and then an aqueous solution of DOX was added. The reaction was carried out at 2-6°C with stirring in the dark. After the reaction was completed, the product was separated by centrifugation to obtain drug-loaded nanoparticles Fe3O4@mPDA-DOX. The drug-loaded nanoparticles Fe3O4@mPDA-DOX were dispersed in deionized water and an aqueous solution of DNase I was added. The reaction was carried out under ice bath conditions with stirring in the dark. After the reaction was completed, the product was magnetically separated to obtain drug-loaded nanoparticles Fe3O4@mPDA-DOX-DNase I. Step S4: Modification of drug-loaded nanoparticles by membrane protein CCDC25 Viral fluid containing CCDC25 was co-incubated with 4T1 cells. After 24 hours of transfection, positive transfected cells were selected and CCDC25-overexpressing 4T1 cells were obtained and labeled as C-4T1 cells. C-4T1 cells were expanded, and extraction reagent A containing a cocktail protease inhibitor was added. After incubation, repeated freeze-thaw cycles were performed to lyse the cells. Cell membrane fragments containing CCDC25 were collected by centrifugation, and membrane protein extraction reagent B was added to fully extract CCDC25 protein. The supernatant of membrane protein CCDC25 was collected by high-speed centrifugation. Membrane protein CCDC25 and drug-loaded nanoparticles Fe3O4@mPDA-DOX-DNase Ⅰ were placed in a liposome extractor, and the product was then separated by magnetic separation to obtain CCDC25-modified drug-loaded nanoparticles, which are drug delivery systems targeting the extracellular trap of neutrophils, and labeled as CCDC25-Fe3O4@mPDA-DOX-DNase Ⅰ.
4. The method for preparing the drug delivery system targeting neutrophil extracellular traps according to claim 3, characterized in that... The specific process of modifying drug-loaded nanoparticles with membrane protein CCDC25 in step S4 is as follows: membrane protein CCDC25 and drug-loaded nanoparticle Fe3O4@mPDA-DOX-DNase Ⅰ are taken at a mass ratio of 1:1000 and protein solution and drug-loaded nanoparticle aqueous solution are prepared respectively. The protein solution and drug-loaded nanoparticle aqueous solution are placed on both sides of the liposome extruder and extruded 8-12 times. Then, magnetic separation is performed to obtain the drug delivery system CCDC25-Fe3O4@mPDA-DOX-DNase Ⅰ.
5. The use of the drug delivery system targeting neutrophil extracellular traps as described in claim 1 or 2 in the preparation of drugs for treating and / or preventing tumors and tumor metastasis.
6. The application according to claim 5, characterized in that... The drug exerts its effects through the following mechanisms: ferric oxide (Fe3O4) is magnetically deposited at the lesion site, increasing local drug concentration; the targeting molecule CCDC25 guides the drug delivery system to specifically accumulate in the neutrophil extracellular trap region of the tumor microenvironment; DNase I degrades the DNA backbone of the neutrophil extracellular trap, disrupting the metastatic microenvironment; the chemotherapeutic drug DOX kills tumor cells; and the mesoporous polydopamine shell generates a photothermal effect under near-infrared light irradiation, killing tumor cells.
7. The application of the drug delivery system targeting neutrophil extracellular traps as described in claim 1 or 2 in the preparation of chemotherapy-photothermal therapy synergistic tumor drugs.