Targeted nanocarriers for the diagnosis and treatment of arterial dissection and their preparation methods

Abstract

This invention discloses a targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method. The targeted nanocarrier is composed of a macromolecular prodrug self-assembly constructed by covalently linking the NLRP3 inhibitor CY-09 and oxidized fucoidan through phenylboronic acid ester bonds and imine bonds, using iodine contrast agent ICA as a connecting bridge. The targeted nanocarrier prepared by this invention possesses good stability, drug release characteristics, excellent dissection targeting, and dual responsiveness to reactive oxygen species and acidic microenvironments, demonstrating significant imaging diagnostic and therapeutic effects on arterial dissection.

Description

Technical Field

[0001] This invention relates to the field of biomedicine, and in particular to a targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method. Background Technology

[0002] Arterial dissection is a rare but extremely serious cardiovascular disease characterized by a tear in the arterial intima, allowing blood to enter the media and forming a subintimal hematoma, which can lead to rapid narrowing of the lumen and severe obstruction of blood flow. If not treated promptly, it can result in arterial rupture or occlusion. Unlike common atherosclerosis, this disease can be triggered by trauma, iatrogenic procedures, or spontaneous factors. Due to its insidious symptoms and complex diagnosis, it is often misdiagnosed as myocardial infarction or angina. Currently, interventional techniques and revascularization therapies (such as stent implantation) remain the primary means of diagnosing and intervening in the acute phase of arterial dissection. However, although interventional procedures can restore blood flow in the short term, as invasive procedures, they still carry certain potential risks, such as widening the dissection, true lumen occlusion, and iatrogenic dissection, and are insufficient to repair vascular damage and inhibit dissection progression at the molecular level. Therefore, there is an urgent need to develop new, non-invasive, higher-resolution imaging and treatment methods for arterial dissection. Elucidating the key molecular and cellular mediators driving the pathogenesis of arterial dissection is crucial for developing targeted and effective treatments. The pathogenesis of arterial dissection is not fully understood, but the main histological changes involve smooth muscle cell phenotypic transformation, extracellular matrix degradation, and inflammatory infiltration. Among these mechanisms, the NLRP3 inflammasome plays a crucial role in the inflammatory response. Researchers have found that the cascade reaction activated by the NLRP3 inflammasome significantly exacerbates vascular inflammation and tissue damage in arterial dissection. Targeted inhibition of its activity can, to some extent, achieve vascular wall stability and repair; however, the non-specific distribution of the drug and its insufficient effective concentration at the lesion site limit its therapeutic efficacy. To improve drug targeting and bioavailability, efficient drug delivery strategies based on nanocarriers have provided new solutions in recent years.

[0003] Nanobiomaterials can serve as drug carriers, enabling better interaction with human cells for precise drug delivery and targeted regulation. By encapsulating or binding diagnostic molecules and drugs within nanoscale material carriers, precise, efficient, and low-toxicity diagnostics and drug delivery can be achieved. Specific targeting molecules can be modified on the surface of nanomedicine delivery systems to allow them to be recognized and taken up by specific cells; however, they generally suffer from problems such as high circulating doses and off-target effects.

[0004] Therefore, constructing a multifunctional nanocarrier that integrates arterial dissection-specific targeting capabilities with diagnostic and therapeutic capabilities is of great clinical significance for the early diagnosis, timely intervention, and reversal of arterial dissection. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention proposes a targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method. The specific technical solution is as follows: A targeted nanocarrier for the diagnosis and treatment of arterial dissection is composed of a macromolecular prodrug constructed by covalently linking the NLRP3 inhibitor CY-09 and oxidized fucoidan through phenylboronic acid ester bonds and imine bonds using iodine contrast agent ICA as a connecting bridge. The structural formula of the macromolecular prodrug is shown below: .

[0006] A method for preparing a targeted nanocarrier for the diagnosis and treatment of arterial dissection includes the following steps: S1: Sodium periodate and fucoidan are dissolved together in deionized water and stirred at room temperature to allow them to react fully, resulting in a first mixed solution; ethylene glycol is added to the first mixed solution and stirred at room temperature to terminate the reaction, resulting in a second mixed solution; the second mixed solution is thoroughly dialyzed in deionized water to remove impurities, and then freeze-dried to obtain oxidized fucoidan; S2: CY-09 drug, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (hereinafter referred to as EDC), and N-hydroxysuccinimide (hereinafter referred to as NHS) are dissolved together in tetrahydrofuran and stirred at room temperature to allow them to react fully, resulting in a third mixed solution; 4-(aminomethyl)phenylboronic acid is added to the third mixed solution, and stirring is continued to allow them to react fully. The mixed solution is purified by silica gel chromatography to obtain phenylboronic acid-modified CY-09; wherein the molar ratio of CY-09, EDC, NHS and 4-(aminomethyl)phenylboronic acid is 1:1.5:1.2:1; S3: The phenylboronic acid-modified CY-09 and iodine contrast agent ICA were dissolved together in dimethyl sulfoxide and stirred at room temperature to allow them to react fully, resulting in a fourth mixed solution; the oxidized fucoidan was dissolved in phosphate buffer solution (hereinafter referred to as PBS) to obtain an oxidized fucoidan solution; the oxidized fucoidan solution was added to the fourth mixed solution, and then added dropwise to the phosphate buffer solution while stirring at room temperature to allow them to react fully, resulting in a fifth mixed solution; the fifth mixed solution was dialyzed thoroughly in deionized water to obtain a targeted nanocarrier for the diagnosis and treatment of arterial dissection.

[0007] Furthermore, in step S1, sodium periodate and fucoidan are dissolved together in deionized water and stirred at room temperature for 12-24 hours to allow them to react fully; the second mixed solution is dialyzed in deionized water for more than 72 hours to remove impurities.

[0008] Furthermore, in S1, the concentration of sodium periodate is 100-200 mM, the concentration of fucoidan is 1-2% w / v, and the concentration of ethylene glycol is 1-2% w / v.

[0009] Further, in S2, CY-09 drug, EDC and NHS are dissolved together in tetrahydrofuran and stirred at room temperature for 12 hours to allow them to react fully, resulting in a third mixed solution; 4-(aminomethyl)phenylboronic acid is added to the third mixed solution, and the reaction is continued to be stirred for 24 hours to allow them to react fully.

[0010] Furthermore, the stirring time in S3 is 12-24 hours, thereby allowing the components constituting the nanoparticles to react fully and to fully self-assemble into nanoparticles in water.

[0011] Furthermore, in S3, the mass ratio of phenylboronic acid-modified CY-09, ICA, and oxidized fucoidan is 5-20:3.5-14:10-40.

[0012] Furthermore, in step S3, the fifth mixed solution is dialyzed thoroughly in deionized water for 24 hours to obtain a targeted nanocarrier for the diagnosis and treatment of aortic dissection.

[0013] Further, in step S3, 5-20g of phenylboronic acid-modified CY-09 and 3.5-14g of iodine contrast agent ICA are dissolved together in 1mL of dimethyl sulfoxide and stirred at room temperature to obtain the fourth mixed solution; 10-40g of the oxidized fucoidan is dissolved in 0.1mL of phosphate buffer solution to obtain the oxidized fucoidan solution; the fourth mixed solution and the oxidized fucoidan solution are mixed and then added dropwise to 1-20mL of phosphate buffer solution and stirred to obtain the fifth mixed solution.

[0014] The beneficial effects of this invention are: (1) The surface-modified oxidized fucoidan of the targeted nanocarrier constructed in this invention has good targeting of arterial dissection and can achieve precise drug delivery to the dissection lesion by binding with activated platelets.

[0015] (2) The imine bond and phenylboronic acid bond in the targeted nanocarrier prepared by the present invention can be synergistically broken in response to the acidic and highly reactive oxygen microenvironment of the lesion area, thereby leading to the dissociation of the nanostructure and the precise release of the drug.

[0016] (3) The iodine contrast agent ICA introduced into the targeted nanocarrier prepared by the present invention can realize X-ray imaging of arterial dissection lesions, thereby playing a role in the diagnosis of arterial dissection.

[0017] (4) The NLRP3 inhibitor CY09 introduced into the targeted nanocarrier prepared in this invention can inhibit inflammation related to the NLRP3 signaling pathway after precise release, thereby inhibiting the abnormal differentiation of macrophages and smooth muscle cells, and ultimately achieving the therapeutic effect of arterial dissection.

[0018] (5) The targeted nanocarrier prepared by the present invention has significantly improved stability, drug release characteristics, excellent sandwich targeting and dual responsiveness to reactive oxygen species and acidic microenvironment. Attached Figure Description

[0019] Figure 1 This is a flowchart of a method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection in an embodiment of the present invention.

[0020] Figure 2 The images shown are the particle size distribution map and transmission electron microscope (TEM) image of the targeted nanocarriers prepared in the embodiments of the present invention, wherein (a) is the particle size distribution map and (b) is the transmission electron microscope (TEM) image.

[0021] Figure 3 This is a particle size distribution diagram of the targeted nanocarrier under different conditions in the embodiments of the present invention.

[0022] Figure 4 This is a diagram showing the in vitro drug release results of the targeted nanocarrier under different conditions in an embodiment of the present invention.

[0023] Figure 5 The figure shows the results of the inhibitory effect of the targeted nanocarrier and CY-09 on NLRP3 in vitro in the embodiments of the present invention.

[0024] Figure 6 This is a diagram showing the targeting performance of the nanocarrier on arterial dissection in animal experiments according to embodiments of the present invention.

[0025] Figure 7 This is a diagnostic imaging result of the nanocarrier on arterial dissection in an animal experiment according to an embodiment of the present invention.

[0026] Figure 8 This is a diagram showing the results of treating arterial dissection with nanocarriers in animal experiments according to an embodiment of the present invention. Detailed Implementation

[0027] The present invention will be described in detail below with reference to the accompanying drawings and preferred embodiments. The objectives and effects of the present invention will become clearer as a result. The present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0028] The design concept of this invention is based on using a "hitchhiking" targeted delivery method to solve problems such as high circulating dose and off-target effects. Due to the impaired vascular intima integrity, exposed subendothelial matrix, and strong local inflammatory response at the site of aortic dissection, functional nanocarriers can achieve specific enrichment at the lesion site through enhanced penetration and retention effects, providing an ideal delivery platform for molecules with diagnostic and therapeutic activity. Studies have shown that fucoidan has a high affinity for P-selectin expressed by activated platelets at the site of aortic dissection and can serve as an excellent targeting molecule, making it possible to achieve precise localization of nanocarriers at the dissection site.

[0029] Example 1 like Figure 1 As shown, this invention proposes a targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method, comprising the following steps: S1: Sodium periodate (200mM) and fucoidan (1% w / v) were dissolved together in deionized water and stirred at room temperature for 12-24h to allow them to react fully, resulting in a first mixed solution; ethylene glycol (1.25% w / v) was added to the first mixed solution and stirred at room temperature to terminate the reaction, resulting in a second mixed solution; the second mixed solution was dialyzed in deionized water for more than 72h to remove impurities, and then freeze-dried to obtain oxidized fucoidan.

[0030] S2: CY-09 (0.423 g, 1 mmol), EDC (0.3 g, 1.5 mmol), and NHS (0.15 g, 1.2 mmol) were dissolved together in tetrahydrofuran and stirred at room temperature for 12 h to allow complete reaction, yielding a third mixed solution. 4-(aminomethyl)phenylboronic acid (0.4 g, 1 mmol) was added to the third mixed solution, and stirring was continued for 24 h to allow complete reaction. The mixed solution was purified by silica gel chromatography to obtain phenylboronic acid-modified CY-09. The molar ratio of CY-09, EDC, NHS, and 4-(aminomethyl)phenylboronic acid was 1:1.5:1.2:1.

[0031] S3: 5 mg of phenylboronic acid-modified CY-09 and 3.5 mg of iodine contrast agent ICA were dissolved together in 1 mL of dimethyl sulfoxide and stirred at room temperature for 12 h to allow for complete reaction, yielding a fourth mixed solution. 10 mg of oxidized fucoidan was dissolved in 0.1 mL of PBS to obtain an oxidized fucoidan solution. This solution was then added to the fourth mixed solution, followed by dropwise addition to 7 mL of PBS, while stirring at room temperature for 2 h to allow for complete reaction, yielding a fifth mixed solution. The fifth mixed solution was dialyzed thoroughly with deionized water for 24 h to prepare a targeted nanocarrier for the diagnosis and treatment of arterial dissection (specifically, through this preparation method, the components combine to obtain a macromolecular prodrug, which automatically shrinks and adjusts its morphology to obtain the targeted nanocarrier).

[0032] The iodine contrast agent ICA is named according to the molecular structure diagram as: 5-amino-N,N'-bis(2,3-dihydroxypropyl)-2,4,6-triiodo-1,3-benzenedicarboxamide.

[0033] The targeted nanocarrier for the diagnosis and treatment of aortic dissection prepared by the above method consists of a macromolecular prodrug constructed by covalently linking the NLRP3 inhibitor CY-09 and oxidized fucoidan through phenylboronic acid ester bonds and imine bonds, using iodine contrast agent ICA as a connecting bridge. The structural formula of the macromolecular prodrug is as follows: Particle size distribution and transmission electron microscopy images of targeted nanocarriers used for the diagnosis and treatment of aortic dissection are shown below. Figure 2 As shown in the figure, the nanocarrier can self-assemble to form uniform particles with nanoscale dimensions.

[0034] Example 2 A targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method, wherein S1 and S2 are the same as in Example 1, and S3 is specifically as follows: 20 mg of phenylboronic acid-modified CY-09 and 14 mg of iodine contrast agent ICA were dissolved together in 1 mL of dimethyl sulfoxide and stirred at room temperature for 12 h to allow for complete reaction, yielding a fourth mixed solution. 40 mg of oxidized fucoidan was dissolved in 0.1 mL of PBS to obtain an oxidized fucoidan solution. This solution was added to the fourth mixed solution, followed by dropwise addition to 7 mL of PBS, and stirred at room temperature for 2 h to allow for complete reaction, yielding a fifth mixed solution. The fifth mixed solution was dialyzed thoroughly with deionized water for 24 h to prepare a targeted nanocarrier for the diagnosis and treatment of arterial dissection.

[0035] Example 3 A targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method, wherein S1 and S2 are the same as in Example 1, and S3 is specifically as follows: 10 mg of phenylboronic acid-modified CY-09 and 7 mg of iodine contrast agent ICA were dissolved together in 1 mL of dimethyl sulfoxide and stirred at room temperature for 24 h to allow for complete reaction, yielding a fourth mixed solution. 20 mg of oxidized fucoidan was dissolved in 0.1 mL of PBS to obtain an oxidized fucoidan solution. This oxidized fucoidan solution was added to the fourth mixed solution, followed by dropwise addition to 7 mL of PBS, while stirring at room temperature for 2 h to allow for complete reaction, yielding a fifth mixed solution. The fifth mixed solution was dialyzed thoroughly with deionized water for 24 h to prepare a targeted nanocarrier for the diagnosis and treatment of arterial dissection.

[0036] Example 4 A targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method, wherein S1 and S2 are the same as in Example 1, and S3 is specifically as follows: 10 mg of phenylboronic acid-modified CY-09 and 3.5 mg of iodine contrast agent ICA were dissolved together in 1 mL of dimethyl sulfoxide and stirred at room temperature for 12 h to allow for complete reaction, yielding a fourth mixed solution. 40 mg of oxidized fucoidan was dissolved in 0.1 mL of PBS to obtain an oxidized fucoidan solution. This oxidized fucoidan solution was added to the fourth mixed solution, followed by dropwise addition to 7 mL of PBS, while stirring at room temperature for 2 h to allow for complete reaction, yielding a fifth mixed solution. The fifth mixed solution was dialyzed thoroughly with deionized water for 24 h to prepare a targeted nanocarrier for the diagnosis and treatment of arterial dissection.

[0037] Example 5 A targeted nanocarrier for the diagnosis and treatment of arterial dissection and its preparation method, wherein S1 and S2 are the same as in Example 1, and S3 is specifically as follows: 5 mg of phenylboronic acid-modified CY-09 and 7 mg of iodine contrast agent ICA were dissolved together in 1 mL of dimethyl sulfoxide and stirred at room temperature for 24 h to allow for complete reaction, yielding a fourth mixed solution. 20 mg of oxidized fucoidan was dissolved in 0.1 mL of PBS to obtain an oxidized fucoidan solution. This oxidized fucoidan solution was added to the fourth mixed solution, followed by dropwise addition to 7 mL of PBS, while stirring at room temperature for 2 h to allow for complete reaction, yielding a fifth mixed solution. The fifth mixed solution was dialyzed thoroughly with deionized water for 24 h to prepare a targeted nanocarrier for the diagnosis and treatment of arterial dissection.

[0038] The effectiveness of the present invention will be further verified through a series of comparative experiments.

[0039] Experimental Example 1: Study on the response of targeted nanocarriers to different concentrations of acid and reactive oxygen species.

[0040] The targeted nanocarriers prepared in Example 1 were placed in phosphate buffer solutions at 37°C under different conditions (pH 7.4, pH 6.5, 0.1 mM H2O2, and pH 6.5 + 0.1 mM H2O2). The particle size changes were measured at regular intervals using dynamic light scattering (DLS). The particle size change results are shown below. Figure 3 As shown.

[0041] Depend on Figure 3It can be seen that the targeted nanocarrier prepared by the present invention exhibits good stability in the pH 7.4 environment. In the pH 6.5 and 0.1 mM H2O2 environment, the targeted nanocarrier gradually decomposes and the particle size increases. In the dual stimulation environment of pH 6.5 + 0.1 mM H2O2, the measured particle size increases significantly, indicating that it has specific response ability under acidic and highly reactive oxygen conditions.

[0042] Experimental Example 2: Study on the in vitro drug release behavior of targeted nanocarriers.

[0043] The targeted nanocarrier prepared in Example 1 was prepared into a solution with a concentration of 0.1 mg / mL. 2 mL of this solution was transferred to a dialysis bag with a molecular weight cutoff of 3500. The dialysis bag was sealed and placed in 500 mL of phosphate buffer solution under different conditions (pH 7.4, pH 6.5, 0.1 mM H2O2, and pH 6.5 + 0.1 mM H2O2). The solution was continuously incubated with shaking at 37°C in the dark. 2 mL of the solution was collected at different time points, and the drug release was measured using high-performance liquid chromatography (HPLC). The results are as follows: Figure 4 As shown.

[0044] Depend on Figure 4 It can be seen that the nanocarrier is structurally stable at pH 7.4 with minimal drug leakage. Under acidic (pH 6.5) or highly reactive oxygen species (0.1 mM H2O2) conditions, the drug release capacity increases significantly. Under the dual stimulation of acidic and highly reactive oxygen species (pH 6.5 + 0.1 mM H2O2), the drug release efficiency is further improved.

[0045] Experimental Example 3: Inhibition of NLRP3 by nanocarriers in vitro.

[0046] In vascular smooth muscle cells and macrophages activated and induced by lipopolysaccharide (50 ng / mL) and nigericin (10 mM), the targeted nanocarrier prepared in Example 1 and the NLRP3 inhibitor (CY-09) were added and co-cultured at 37°C for 4.5 h. The cells were then subjected to NLRP3 immunofluorescence staining, and the NLRP3 fluorescence signal was observed under a fluorescence microscope.

[0047] Depend on Figure 5 It can be seen that, compared with the NLRP3 inhibitor (CY-09), vascular smooth muscle cells and macrophages treated with the prepared targeted nanocarrier showed weaker NLRP3 fluorescence signals, indicating that it has a stronger inhibitory effect on NLRP3.

[0048] Experiment 4: Animal experiments to verify the targeting performance of nanocarriers on arterial dissection.

[0049] A mouse model of aortic dissection was established. Mice were injected via the tail vein with equal volumes of physiological saline (blank control), DiI-labeled nanocarriers without oxidized fucoidan, and the targeted nanocarrier prepared in Example 1 of this invention. The drug dosage was 10 mg / kg per mouse. Mice were sacrificed at 6, 12, and 24 hours, and the aorta was dissected. Fluorescence intensity was measured using an IVIS spectroscopy system.

[0050] Depend on Figure 6 It can be seen that the intact targeted nanocarriers have more specific enrichment at the arterial dissection, and the enriched targeted nanocarriers increase significantly with time, indicating that they have better targeting performance for arterial dissection.

[0051] Experimental Example 5: Animal experiments to verify the diagnostic efficacy of nanocarriers for arterial dissection lesions.

[0052] A mouse model of aortic dissection was established. Equal volumes of physiological saline (blank control), nanocarriers without oxidized fucoidan (10 mg / kg), and targeted nanocarriers prepared in Example 1 of this invention (10 mg / kg) were injected via the tail vein. Mice were sacrificed after 24 hours, and the aorta was dissected for X-CT angiography. The experimental results are as follows: Figure 7 As shown.

[0053] Depend on Figure 7 It can be seen that, compared with the nanocarriers without oxidized fucoidan, the targeted nanocarriers prepared in Example 1 have better X-CT arterial dissection imaging effect, and the X-ray signal of the lesion site is significantly enhanced, which effectively improves the imaging resolution.

[0054] Experiment 6: Animal experiments to verify the therapeutic effect of nanocarriers on arterial dissection lesions.

[0055] A mouse model of arterial dissection was established. The mice were injected via the tail vein every other day with either the nanocarrier prepared in Example 1 (10 mg / kg / dose), an uncoated fucoidan nanocarrier (10 mg / kg / dose), the NLRP3 inhibitor CY-09 (1 mg / kg / dose), or an equal volume of physiological saline. After two weeks of continuous treatment, the mouse aorta was isolated, and sections of the arterial dissection site were prepared for HE staining, masson staining, and elastin (EVG) staining. The experimental results are as follows: Figure 8 As shown.

[0056] Depend on Figure 8 It can be seen that, compared with the incomplete nanocarrier, the targeted nanocarrier prepared in Example 1 has a better effect on inhibiting the formation of arterial dissection and can reverse the formed arterial dissection.

[0057] The targeted nanocarrier prepared by the method of this invention can specifically target and bind to activated platelets in circulation via oxidized fucoidan, achieving precise enrichment at the site of arterial dissection lesions. Simultaneously, it exhibits excellent specific responsiveness to reactive oxygen species (ROS) and acidic microenvironments, allowing for the release of encapsulated drugs (i.e., the NLRP3 inhibitor CY-09) through the cleavage of chemical bonds under highly reactive ORS and acidic environments. The therapeutic effect is achieved by utilizing the drug's inhibitory effect on the NLRP3 pathway. In summary, the targeted nanocarrier prepared by the method of this invention, possessing good stability, drug release characteristics, excellent dissection targeting, and dual responsiveness to ROS and acidic microenvironments, demonstrates significant imaging diagnostic and therapeutic effects for arterial dissection.

[0058] It will be understood by those skilled in the art that the above descriptions are merely preferred examples of the invention and are not intended to limit the invention. Although the invention has been described in detail with reference to the foregoing examples, those skilled in the art can still modify the technical solutions described in the foregoing examples or make equivalent substitutions for some of the technical features. All modifications and equivalent substitutions made within the spirit and principles of the invention should be included within the scope of protection of the invention.

Claims

1. A targeted nanocarrier for the diagnosis and treatment of arterial dissection, characterized in that, It is composed of a macromolecular prodrug self-assembly constructed by using iodine contrast agent ICA as a connecting bridge and covalently linking NLRP3 inhibitor CY-09 and oxidized fucoidan through phenylboronic acid ester bonds and imine bonds; The structural formula of the macromolecular prodrug is shown below: 。 2. A method for preparing a targeted nanocarrier for the diagnosis and treatment of arterial dissection, characterized in that, Includes the following steps: S1: Sodium periodate and fucoidan are dissolved together in deionized water and stirred at room temperature to allow them to react fully, resulting in a first mixed solution; ethylene glycol is added to the first mixed solution and stirred at room temperature to terminate the reaction, resulting in a second mixed solution; the second mixed solution is thoroughly dialyzed in deionized water to remove impurities, and then freeze-dried to obtain oxidized fucoidan; S2: CY-09 drug, EDC, and NHS are dissolved together in tetrahydrofuran and stirred at room temperature to allow them to react fully, yielding a third mixed solution; 4-(aminomethyl)phenylboronic acid is added to the third mixed solution, and stirring is continued to allow them to react fully. The mixed solution is purified by silica gel chromatography to obtain phenylboronic acid-modified CY-09; wherein the molar ratio of CY-09, EDC, NHS, and 4-(aminomethyl)phenylboronic acid is 1:1.5:1.2:1; S3: The phenylboronic acid-modified CY-09 and iodine contrast agent ICA are dissolved together in dimethyl sulfoxide and stirred at room temperature to allow them to react fully, resulting in a fourth mixed solution; the oxidized fucoidan is dissolved in phosphate buffer solution to obtain an oxidized fucoidan solution; the oxidized fucoidan solution is added to the fourth mixed solution, and then added dropwise to the phosphate buffer solution while stirring at room temperature to allow them to react fully, resulting in a fifth mixed solution; the fifth mixed solution is thoroughly dialyzed with deionized water to obtain a targeted nanocarrier for the diagnosis and treatment of arterial dissection.

3. The method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection according to claim 2, characterized in that, In step S1, sodium periodate and fucoidan are dissolved together in deionized water and stirred at room temperature for 12-24 hours to allow them to react fully; the second mixed solution is dialyzed in deionized water for more than 72 hours to remove impurities.

4. The method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection according to claim 2, characterized in that, In S1, the concentration of sodium periodate is 100-200 mM, the concentration of fucoidan is 1-2% w / v, and the concentration of ethylene glycol is 1-2% w / v.

5. The method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection according to claim 2, characterized in that, In S2, CY-09 drug, EDC and NHS are dissolved together in tetrahydrofuran and stirred at room temperature for 12 hours to allow them to react fully, resulting in a third mixed solution; 4-(aminomethyl)phenylboronic acid is added to the third mixed solution and the reaction is continued for 24 hours to allow it to react fully.

6. The method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection according to claim 2, characterized in that, In step S3, the stirring time for obtaining the fourth mixed solution is 12-24 hours, thereby allowing the components constituting the nanoparticles to react fully and to fully self-assemble in water to form nanoparticles.

7. The method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection according to claim 2, characterized in that, In S3, the mass ratio of phenylboronic acid-modified CY-09, ICA and oxidized fucoidan is 5-20:3.5-14:10-40.

8. The method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection according to claim 2, characterized in that, In step S3, the fifth mixed solution is dialyzed in deionized water for 24 hours to obtain a targeted nanocarrier for the diagnosis and treatment of arterial dissection.

9. The method for preparing targeted nanocarriers for the diagnosis and treatment of arterial dissection according to claim 2, characterized in that, In step S3, 5-20g of phenylboronic acid-modified CY-09 and 3.5-14g of iodine contrast agent ICA are dissolved together in 1mL of dimethyl sulfoxide and stirred at room temperature to obtain the fourth mixed solution; 10-40g of the oxidized fucoidan is dissolved in 0.1mL of phosphate buffer solution to obtain the oxidized fucoidan solution; the fourth mixed solution and the oxidized fucoidan solution are mixed and then added dropwise to 1-20mL of phosphate buffer solution and stirred to obtain the fifth mixed solution.

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