A core-shell magnetic nanocarrier, a preparation method and application thereof

Abstract

The application discloses a kind of core-shell magnetic nano-carrier and its preparation method and application, belong to nano-carrier technical field, the nano-carrier has hollow core-shell structure, it is prepared by following method: after Fe3O4@SiO2 Nanoparticle is mixed with the solution of NH4Cl, the solution of MnCl2·H2O, ammonia water, Fe3O4@MnSiO3 is prepared by hydrothermal reaction, the Fe3O4@MnSiO3 is obtained by acid treatment, washing, and has hollow structure core-shell magnetic nano-carrier.The core-shell magnetic nano-drug carrier prepared in the application has hollow structure, drug loading capacity is sufficient, and has magnetic adsorption and magnetic targeting capacity, can be used as general drug targeting delivery carrier;And the preparation method of the application is simple, and the nano-carrier material prepared has good biocompatibility, clear structure, low cost, can deliver a variety of drug molecules, has wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of nanocarrier technology, specifically relating to a core-shell magnetic nanocarrier, its preparation method, and its application. Background Technology

[0002] Nanocarriers, with their unique size effect, surface modification flexibility, and controllable drug delivery, have become one of the core directions for optimizing drug therapeutic effects and promoting the development of combination therapies. Compared with traditional free drug delivery modes, nanocarriers can achieve efficient co-delivery of drugs with complementary mechanisms of action, effectively coordinating the pharmacokinetic behavior of each drug in vivo, improving the synergistic effect efficiency of drugs at the lesion site, and opening up new pathways for the precision treatment of complex diseases with multiple factors, such as tumors.

[0003] While nanotechnology has demonstrated significant advantages in co-delivering multiple drugs to enhance the efficacy of combined therapies, existing nanomedicine delivery systems still face two major challenges. First, the structural limitations of nanocarriers themselves, such as dense core-shell structures or limited internal space, generally result in insufficient drug loading, failing to meet the high drug loading requirements of multi-drug combination therapies and thus limiting the full realization of synergistic therapeutic effects. Second, in vivo targeted delivery efficiency is low. After systemic administration, nanocarriers often fail to accumulate sufficiently at the tumor site during delivery, leading to premature excessive release of drugs in the bloodstream or accumulation in normal tissues, causing severe off-target effects and resulting in systemic toxicity.

[0004] Therefore, developing a universal, precise, and synergistic delivery nanocarrier with a reasonable structural design, sufficient drug loading capacity, and significant magnetic targeting capability is of vital importance for combined anti-tumor therapy. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention aims to provide a core-shell magnetic nanocarrier, its preparation method, and its application.

[0006] To achieve the above objectives, a first aspect of the present invention provides a core-shell magnetic nanocarrier having a hollow core-shell structure, which is prepared by the following method: Fe3O4@SiO2 nanoparticles were mixed with NH4Cl solution, MnCl2·H2O solution and ammonia water and then subjected to hydrothermal reaction to obtain Fe3O4@MnSiO3. The Fe3O4@MnSiO3 was then treated with acid and washed to obtain a core-shell magnetic nanocarrier with a hollow structure of MnSiO3 shell and Fe3O4 core. The mass ratio of Fe3O4@SiO2 nanoparticles, NH4Cl, MnCl2·H2O to ammonia water is 100mg:(160~200)mg:(30~60)mg:(390~500)μL.

[0007] A second aspect of the present invention provides a method for preparing the above-mentioned core-shell magnetic nanocarrier, comprising the following steps: NH4Cl and MnCl2·H2O were added to water, dissolved, and then ammonia was added. Fe3O4@SiO2 nanoparticles were then added and stirred until homogeneous to obtain a mixture. The mixture was subjected to a hydrothermal reaction. After the reaction was completed, it was cooled to ambient temperature. The products were separated by an external magnetic field and washed to obtain Fe3O4@MnSiO3. The obtained Fe3O4@MnSiO3 was subjected to acid treatment, and the acid-treated product was washed three times with deionized water to obtain a core-shell magnetic nanocarrier, denoted as CS NPs carrier.

[0008] Furthermore, the hydrothermal reaction temperature is 140℃~180℃, and the hydrothermal reaction time is 14h~20h.

[0009] Furthermore, the acid used in the acid treatment is any one of hydrofluoric acid, hydrochloric acid, sulfuric acid, or acetic acid with a mass concentration of 4% to 10%.

[0010] Furthermore, the acid treatment time is 1 hour to 4 hours.

[0011] A third aspect of the present invention is to provide the application of the above-described core-shell magnetic nanocarrier in the preparation of a drug delivery system.

[0012] Furthermore, the drug delivery system is used to carry one or more of antitumor drugs or fluorescent molecules.

[0013] Furthermore, the antitumor drug is doxorubicin; the fluorescent molecule is any one or more of indocyanine green, fluorescein isothiocyanate, and rhodamine B.

[0014] Compared with the prior art, the present invention has the following beneficial effects: (1) In this invention, Fe3O4@SiO2 nanoparticles, NH4Cl, MnCl2·H2O and ammonia water are mixed in a mass ratio of 100mg:(160~200)mg:(30~60)mg:(390~500)μL to prepare Fe3O4@MnSiO3 by hydrothermal reaction. Then, the core-shell magnetic nanocarrier is obtained by acid treatment and washing. Using NH4Cl as an etchant, and under precise control of the raw material ratio and ammonia dosage, a non-hollow Fe3O4@SiO2 was transformed into a hollow Fe3O4@MnSiO3 magnetic nanocarrier through an "inside-out" template method. This carrier has Fe3O4 as the core and MnSiO3 as the shell. Its hollow structure provides a huge internal cavity, giving it sufficient drug loading capacity and enabling efficient co-loading of anti-tumor drugs, fluorescent probes, and other therapeutic molecules. Meanwhile, throughout the reaction process, the complete magnetism of the Fe3O4 core was successfully preserved through the mild alkaline environment provided by ammonia and precise process control. The formation of the MnSiO3 shell also served as a protective layer, preventing the oxidation or aggregation of Fe3O4 in the physiological environment. The complete Fe3O4 core has magnetic adsorption properties, enabling the carrier to have significant active targeting capabilities under the guidance of an external magnetic field. When the carrier reaches the lesion site, the dense MnSiO3 shell acts as a "drug sustained-release reservoir," effectively delaying drug diffusion through physical barrier action. This achieves "continuous drug delivery" and "effectively avoids premature drug release and off-target effects," thereby significantly reducing systemic toxicity.

[0015] (2) The method of the present invention is simple and low in cost. The prepared nanocarrier material has good biocompatibility, stable structure and clear composition, and can be adapted to drug molecules with different physicochemical properties. It has the value of being promoted as a universal drug delivery carrier in the field of targeted combination therapy. Attached Figure Description

[0016] Figure 1 The images show scanning electron microscope (SEM) and transmission electron microscope (TEM) images of Fe3O4, Fe3O4@SiO2, Fe3O4@MnSiO3, and the CS NPs nanocarriers obtained after acid treatment in Example 1 of this invention; where a is the SEM image of Fe3O4; b is the SEM image of Fe3O4@SiO2; c is the SEM image of Fe3O4@MnSiO3; d is the TEM image of Fe3O4@MnSiO3 nanocarriers; and e is the TEM image of CS NPs.

[0017] Figure 2 The particle size analysis diagram shows the Fe3O4@MnSiO3 and CS NPs nanocarriers prepared in Example 1 of this invention.

[0018] Figure 3 This is a Zeta potential diagram of the Fe3O4@MnSiO3 and CS NPs nanocarriers prepared in Example 1 of the present invention.

[0019] Figure 4 The image shows the hysteresis loop of the CS NPs nanocarrier prepared in Example 1 of this invention.

[0020] Figure 5 This is a schematic diagram of the magnetic adsorption nanoparticle movement of the CS NPs nanocarrier prepared in Example 1 of the present invention.

[0021] Figure 6 The images show the UV absorption spectra of doxorubicin (DOX), indocyanine green (ICG), fluorescein isothiocyanate (FITC), and rhodamine B (RhB) supported on the CS NPs nanocarriers prepared in Example 1 and the Fe3O4@MnSiO3 nanocarriers prepared in the comparative example, as well as the fluorescent molecules. Specifically, a) shows the UV spectrum of DOX supported on the CS NPs nanocarriers obtained in Example 1 and the Fe3O4@MnSiO3 nanocarriers obtained in the comparative example; b) shows the UV spectrum of ICG supported on the C-SNPs nanocarriers obtained in Example 1 and the Fe3O4@MnSiO3 nanocarriers obtained in the comparative example; c) shows the UV spectrum of FITC supported on the CS NPs nanocarriers obtained in Example 1 and the Fe3O4@MnSiO3 nanocarriers obtained in the comparative example; and d) shows the UV spectrum of RhB supported on the CS NPs nanocarriers obtained in Example 1 and the Fe3O4@MnSiO3 nanocarriers obtained in the comparative example. Detailed Implementation

[0022] To enable those skilled in the art to better understand and implement the technical solutions of the present invention, the present invention will be further described below in conjunction with specific embodiments and accompanying drawings.

[0023] Unless otherwise specified, all reagents used in this invention are commercially available, and all methods used are conventional techniques in the art.

[0024] Example 1 A method for preparing core-shell magnetic nanomaterials includes the following steps: First, 0.1672 g of NH4Cl and 36 mg of MnCl2·H2O were added to 10 mL of deionized water, followed by 0.39 mL of ammonia. Then, 0.1 g of Fe3O4@SiO2 was mixed and stirred for 30 min. The mixture was then transferred to an autoclave and heat-treated at 140 °C for 14 h, followed by natural cooling to ambient temperature. Subsequently, the Fe3O4@MnSiO3 product was separated using an external magnetic field and washed three times with deionized water. The Fe3O4@MnSiO3 was then treated with an acid solution, specifically 4% hydrofluoric acid, for 2 h. The acid-treated product was then washed three times with deionized water to obtain the core-shell magnetic nanocarrier, i.e., the CS NPs carrier.

[0025] Example 2 A method for preparing core-shell magnetic nanomaterials is the same as that in Example 1, except that the proportions of the various substances used to prepare Fe3O4@MnSiO3 are different, and the method includes the following steps: First, 0.2 g of NH4Cl and 60 mg of MnCl2·H2O were added to 10 mL of deionized water, followed by 0.5 mL of ammonia. Then, 0.1 g of Fe3O4@SiO2 was mixed and stirred for 30 min. The mixture was then transferred to an autoclave and heat-treated at 140 °C for 14 h, followed by natural cooling to ambient temperature. Subsequently, the Fe3O4@MnSiO3 product was separated using an external magnetic field and washed three times with deionized water. The Fe3O4@MnSiO3 was then treated with an acid solution, specifically 4% hydrofluoric acid, for 2 h. The acid-treated product was then washed three times with deionized water to obtain the core-shell magnetic nanocarrier, i.e., the CS NPs carrier.

[0026] Example 3 A method for preparing core-shell magnetic nanomaterials is the same as that in Example 1, except that the 4% hydrofluoric acid used in the acid treatment is replaced with 4% hydrochloric acid, and the treatment time is changed to 1 hour. The method includes the following steps: First, 0.1672 g of NH4Cl and 36 mg of MnCl2·H2O were added to 10 mL of deionized water, followed by 0.39 mL of ammonia. Then, 0.1 g of Fe3O4@SiO2 was mixed and stirred for 30 min. The mixture was then transferred to an autoclave and heat-treated at 140 °C for 14 h, followed by natural cooling to ambient temperature. Subsequently, the Fe3O4@MnSiO3 product was separated using an external magnetic field and washed three times with deionized water. The Fe3O4@MnSiO3 was then treated with an acid solution, specifically 4% hydrochloric acid, for 1 h. The acid-treated product was then washed three times with deionized water to obtain the core-shell magnetic nanocarrier, i.e., the CS NPs carrier.

[0027] Example 4 A method for preparing core-shell magnetic nanomaterials is the same as that in Example 1, except that the 4% hydrofluoric acid used in the acid treatment is replaced with 4% sulfuric acid, and includes the following steps: First, 0.1672 g of NH4Cl and 36 mg of MnCl2·H2O were added to 10 mL of deionized water, followed by 0.39 mL of ammonia. Then, 0.1 g of Fe3O4@SiO2 was mixed and stirred for 30 min. The mixture was then transferred to an autoclave and heat-treated at 140 °C for 14 h, followed by natural cooling to ambient temperature. Subsequently, the Fe3O4@MnSiO3 product was separated using an external magnetic field and washed three times with deionized water. The Fe3O4@MnSiO3 was then treated with an acid solution, specifically 4% sulfuric acid, for 2 h. The acid-treated product was then washed three times with deionized water to obtain the core-shell magnetic nanocarrier, i.e., the CS NPs carrier.

[0028] Example 5 A method for preparing core-shell magnetic nanomaterials is the same as that in Example 1, except that the 4% hydrofluoric acid used in the acid treatment is replaced with 4% acetic acid, and the treatment time is changed to 3.5 hours. The method includes the following steps: First, 0.1672 g of NH4Cl and 36 mg of MnCl2·H2O were added to 10 mL of deionized water, followed by 0.39 mL of ammonia. Then, 0.1 g of Fe3O4@SiO2 was mixed and stirred for 30 min. The mixture was then transferred to an autoclave and heat-treated at 140 °C for 14 h, followed by natural cooling to ambient temperature. Subsequently, the Fe3O4@MnSiO3 product was separated using an external magnetic field and washed three times with deionized water. The Fe3O4@MnSiO3 was then treated with an acid solution, specifically 4% acetic acid, for 3.5 h. The acid-treated product was then washed three times with deionized water to obtain the core-shell magnetic nanocarrier, i.e., the CS NPs carrier.

[0029] Example 6 A method for preparing core-shell magnetic nanomaterials is the same as that in Example 1, except that the hydrothermal reaction temperature is changed from 140 °C to 180 °C, and includes the following steps: First, 0.1672 g of NH4Cl and 36 mg of MnCl2·H2O were added to 10 mL of deionized water, followed by 0.39 mL of ammonia. Then, 0.1 g of Fe3O4@SiO2 was mixed and stirred for 30 min. The mixture was then transferred to an autoclave and heat-treated at 180 °C for 14 h, followed by natural cooling to ambient temperature. Subsequently, the Fe3O4@MnSiO3 product was separated using an external magnetic field and washed three times with deionized water. The Fe3O4@MnSiO3 was then treated with an acid solution, specifically 4% hydrofluoric acid, for 2 h. The acid-treated product was then washed three times with deionized water to obtain the core-shell magnetic nanocarrier, i.e., the CS NPs carrier.

[0030] Comparative Example Nanomaterials were prepared according to the preparation method of Example 1, except that the acid treatment step was omitted. The specific steps are as follows: First, 0.1672 g of NH4Cl and 36 mg of MnCl2·H2O were added to 10 mL of deionized water, followed by 0.39 mL of ammonia. Then, 0.1 g of Fe3O4@SiO2 was mixed and stirred for 30 min. The mixture was then transferred to an autoclave and heat-treated at 140 °C for 14 h. The system was then allowed to cool naturally to ambient temperature. Subsequently, the Fe3O4@MnSiO3 product was separated using an external magnetic field and washed three times with deionized water to obtain the Fe3O4@MnSiO3 nanocarrier.

[0031] Results Analysis Figure 1Figures a, b, and c are scanning electron microscope (SEM) images of Fe3O4, Fe3O4@SiO2, and Fe3O4@MnSiO3 in Example 1, respectively; figures d and e are transmission electron microscope (TEM) images of Fe3O4@MnSiO3 and CS NPs in Example 1, respectively. The morphology of different materials can be observed through SEM and TEM results. TEM clearly shows that, compared to the comparative example, CS NPs, a material with a hollow core-shell structure, was obtained after acid treatment.

[0032] Figure 2 The results show the nanoparticle sizes of four materials: Fe3O4, Fe3O4@SiO2, Fe3O4@MnSiO3, and CS NPs. These results reveal the differences in nanoparticle size among the different materials. The particle size of the materials loaded with Si ions, Mn ions, and those treated with acid is significantly larger than that of basic Fe3O4. This indicates that the acid-treated materials have more space to support different drugs.

[0033] Figure 3 The results of the Zeta potentials of the four materials Fe3O4, Fe3O4@SiO2, Fe3O4@MnSiO3 and CS NPs in Example 1 are shown. It can be seen that, compared with the comparative example, the acid-treated material CS NPs can increase the positive charge of the material, raising the potential of the entire material to -15 mV to -20 mV.

[0034] Figure 4 The hysteresis loop results of the CS NPs material obtained in Example 1 are shown, proving that the material is magnetic and can play a magnetic guiding role. This indicates that in practical applications, it can carry anti-tumor drugs and use the magnetic guiding role of the material to perform magnetic targeting, thereby enhancing the targeting of anti-tumor drugs.

[0035] Figure 5 The results of Example 1 demonstrate that the CS NPs material obtained can be attracted by a magnet, which also proves that the material has magnetic adsorption properties, indicating that in practical applications, the material has magnetic targeting properties after loading anti-tumor drugs.

[0036] Figure 6 The UV absorption spectra of the CS NPs nanocarrier obtained in Example 1 and the Fe3O4@MnSiO3 nanocarrier obtained in the comparative example, supporting drugs such as DOX, ICG, FIGC, and RhB, as well as fluorescent molecules, are shown. Figure 6It can be seen that the CS NPs nanocarrier obtained by the present invention can carry more different types of drugs and fluorescent molecules compared with the Fe3O4@MnSiO3 nanocarrier obtained by the comparative example. At the same time, the drug loading of the CS NPs nanomaterial obtained by acid treatment of the present invention is greater than that of the Fe3O4@MnSiO3 nanocarrier obtained without acid treatment in the comparative example.

[0037] It should be noted that when numerical ranges are involved in this invention, it should be understood that both endpoints of each numerical range and any value between the two endpoints can be selected. Since the steps and methods used are the same as in the embodiments, preferred embodiments are described in this invention to avoid redundancy. Although preferred embodiments of this invention have been described, those skilled in the art, once they understand the inventive concept of this invention, can make other changes and modifications to these embodiments, and all such changes and modifications fall within the scope of this invention.

[0038] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. If such modifications and variations fall within the scope of equivalents of this invention, then this invention also intends to include these modifications and variations.

Claims

1. A core-shell magnetic nanocarrier, characterized in that, The nanocarrier has a hollow core-shell structure and is prepared by the following method: Fe3O4@SiO2 nanoparticles were mixed with NH4Cl solution, MnCl2·H2O solution and ammonia water and then subjected to hydrothermal reaction to obtain Fe3O4@MnSiO3. The Fe3O4@MnSiO3 was then treated with acid and washed to obtain a core-shell magnetic nanocarrier with a hollow structure of MnSiO3 shell and Fe3O4 core. The mass ratio of Fe3O4@SiO2 nanoparticles, NH4Cl, and MnCl2·H2O to ammonia water is 100mg:(160~200)mg:(30~60)mg:(390~500)μL. The acid used in the acid treatment is any one of hydrofluoric acid, hydrochloric acid, sulfuric acid or acetic acid with a mass concentration of 4% to 10%. The acid treatment time is 1 hour to 4 hours.

2. A method for preparing the core-shell magnetic nanocarrier as described in claim 1, characterized in that, Includes the following steps: NH4Cl and MnCl2·H2O were added to water and dissolved. Ammonia water was then added, followed by Fe3O4@SiO2 nanoparticles. The mixture was stirred and mixed evenly to obtain a mixture. The mixture was subjected to a hydrothermal reaction. After the reaction was completed, it was cooled to ambient temperature. The products were separated using an external magnetic field and washed to obtain Fe3O4@MnSiO3. The obtained Fe3O4@MnSiO3 was subjected to acid treatment, and the acid-treated product was washed three times with deionized water to obtain a core-shell magnetic nanocarrier.

3. The method for preparing the core-shell magnetic nanocarrier according to claim 2, characterized in that, The hydrothermal reaction temperature is 140℃~180℃, and the hydrothermal reaction time is 14h~20h.

4. The application of the core-shell magnetic nanocarrier as described in claim 1 in the preparation of a drug delivery system.

5. The application according to claim 4, characterized in that, The drug delivery system is used to carry one or more of antitumor drugs or fluorescent molecules.

6. The application according to claim 5, characterized in that, The antitumor drug is doxorubicin; the fluorescent molecule is any one or more of indocyanine green, fluorescein isothiocyanate, and rhodamine B.

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