Mesoporous nanomaterial coupled with CCR2 antibody as well as preparation method and application of mesoporous nanomaterial

Abstract

The invention relates to the technical field of drug carriers, in particular to a mesoporous nanomaterial coupled with a CCR2 antibody and a preparation method and application of the mesoporous nanomaterial. According to the invention, the aminated mesoporous material is used for loading the drug and is coupled with the CCR2 antibody, so that the obtained CCR2 antibody coupled mesoporous nano material can target CCR2 + macrophages, the bioavailability of drugs such as matrine is improved, and the side effect is reduced. According to the invention, leading-edge technical elements such as a mesoporous nano-carrier, CCR2 antibody targeted modification and macrophage precise delivery are introduced, so that a carrier-drug-antibody ternary innovative combination system is formed.

Description

Technical Field

[0001] This invention relates to the field of drug carrier technology, specifically to mesoporous nanomaterials conjugated with CCR2 antibodies, their preparation methods, and applications. Background Technology

[0002] Matrine (MAT) is a bioactive component extracted from the traditional Chinese medicine Sophora flavescens. It possesses various pharmacological effects, including anti-inflammatory, antioxidant, antitumor, antifibrotic, and antiviral properties, and has been used clinically to treat tumors, chronic hepatitis, radiation-induced lung injury, eczema, dysentery, and pruritus. However, multiple studies have reported that MAT can cause hepatotoxicity, nephrotoxicity, neurotoxicity, and even cardiotoxicity, severely limiting its therapeutic efficacy and application. One significant reason for its side effects is the systemic effect of high-dose medication. Therefore, finding ways to improve the bioavailability of MAT and reduce its side effects is urgently needed.

[0003] Nanomedicines, as novel drug delivery systems, offer advantages such as improved drug stability and solubility, reduced side effects, enhanced bioavailability, and precise drug release to lesion sites. However, macrophages (MAT) suffer from low bioavailability, poor chemical stability, and significant side effects. Therefore, constructing MAT-loaded nanomedicines and targeting their delivery to macrophages holds promise for improving the therapeutic efficacy of MAT and reducing side effects.

[0004] CCR2+ macrophages are macrophages that express chemokine receptor 2 (CC Chemokine Receptor 2). They can be recruited to sites of inflammation or injury, exhibiting a pro-inflammatory phenotype (M1 type). Upon activation, they produce and release large amounts of pro-inflammatory factors and participate in antigen presentation; however, overactivation can lead to tissue damage. Targeting CCR2+ macrophages is an important strategy for treating inflammatory damage in the body. Therefore, constructing MAT nanomedicines that target CCR2+ macrophages may further enhance therapeutic efficacy and reduce side effects. Summary of the Invention

[0005] Based on this, the present invention provides mesoporous nanomaterials conjugated with CCR2 antibodies, their preparation methods and applications, thereby solving at least one problem in the prior art.

[0006] In a first aspect, the present invention provides a method for preparing mesoporous nanomaterials conjugated with CCR2 antibodies, comprising the following steps: Amination of mesoporous materials yields amination-modified mesoporous materials. The drug is loaded onto the aminated mesoporous material to obtain the drug-loaded aminated mesoporous material; CCR2 antibody was coupled with drug-loaded aminated mesoporous material to obtain CCR2 antibody-coupled mesoporous nanomaterial.

[0007] Secondly, the present invention provides a mesoporous nanomaterial conjugated with a CCR2 antibody, which is obtained by the above-mentioned method for preparing mesoporous nanomaterial conjugated with a CCR2 antibody.

[0008] Thirdly, the present invention provides the application of the above-mentioned mesoporous nanomaterials conjugated with CCR2 antibodies in the preparation of drugs targeting CCR2+ macrophages.

[0009] Fourthly, the present invention provides a drug targeting CCR2+ macrophages, comprising the above-mentioned mesoporous nanomaterial conjugated with a CCR2 antibody.

[0010] Due to the adoption of the above technical solutions, the embodiments of the present invention have at least the following beneficial effects: (1) Mesoporous nanomaterials utilize the specific high expression of CCR2 receptor on the surface of macrophages to significantly increase the drug concentration in target cells while avoiding damage to normal cells and other organs, thus greatly reducing systemic toxic side effects. (2) The particle size of mesoporous nanomaterials ensures sufficient drug loading space to achieve efficient drug loading, and also facilitates cell internalization and tissue penetration; (3) The excellent biocompatibility and biodegradability of mesoporous nanomaterials ensure safety, and silicates are eventually metabolized into non-toxic silicic acid and excreted in urine. (4) The drug is protected by mesoporous nanomaterial carriers to avoid degradation in the gastrointestinal tract and blood, thereby improving bioavailability; the sustained release property prolongs the drug's action time and reduces the frequency of administration; (5) The enhanced permeation and retention (EPR) effect of mesoporous nanomaterials further improves drug accumulation in the damaged area; (6) Targeted delivery of mesoporous nanomaterials significantly reduces the distribution of drugs in organs such as the liver and kidneys, thereby reducing the risk of liver and kidney toxicity; nanoencapsulation and protection reduce direct contact between drugs and normal tissues; the good biocompatibility of the carrier material avoids immunogenic reactions, and the drug can be repeatedly administered without producing significant immune rejection. Attached Figure Description

[0011] Figure 1 This is a TEM image of aminated mesoporous SiO2 in an embodiment of the present invention.

[0012] Figure 2 This is a SEM image of aminated mesoporous SiO2 in an embodiment of the present invention.

[0013] Figure 3 This is an EDS image of aminated mesoporous SiO2 in an embodiment of the present invention.

[0014] Figure 4 The image shows the energy dispersive spectroscopy (EDS) results of aminated mesoporous SiO2 in this embodiment of the invention.

[0015] Figure 5 This is a TEM image of aminated mesoporous SiO2 loaded with matrine in an embodiment of the present invention.

[0016] Figure 6 This is a HAADF STEM image of aminated mesoporous SiO2 loaded with matrine in an embodiment of the present invention.

[0017] Figure 7 This is an elemental mapping diagram of aminated mesoporous SiO2 loaded with matrine in an embodiment of the present invention.

[0018] Figure 8 This is an energy dispersive spectroscopy (EDS) result of aminated mesoporous SiO2 loaded with matrine in an embodiment of the present invention.

[0019] Figure 9 This is a SEM image of aminated mesoporous SiO2 loaded with matrine in an embodiment of the present invention.

[0020] Figure 10 This is an EDS image of aminated mesoporous SiO2 loaded with matrine in an embodiment of the present invention.

[0021] Figure 11 The infrared spectra of aminated mesoporous SiO2, aminated mesoporous SiO2 loaded with matrine, and mesoporous silica nanoparticles coupled with CCR2 antibody are shown in the embodiments of the present invention.

[0022] Figure 12 The particle size distribution and surface charge characteristics of aminated mesoporous silica (SiO2-NH2) before and after loading with matrine are shown in the embodiments of the present invention.

[0023] Figure 13 The images show the ultraviolet absorption spectra of matrine loaded with different concentrations in the embodiments of the present invention.

[0024] Figure 14 This is a standard curve showing the relationship between matrine concentration and absorbance in an embodiment of the present invention.

[0025] Figure 15 The image shows the UV absorption spectra of SiO2-NH2 before and after drug loading in an embodiment of the present invention. Detailed Implementation

[0026] The following will provide a clear and complete description of the concept and technical effects of the present invention, so as to fully explain the purpose, solution and effects of the present invention.

[0027] Although matrine has various pharmacological effects, its side effects severely limit its therapeutic efficacy and application. To improve the bioavailability of matrine and other drugs and reduce side effects, this invention provides a mesoporous nanomaterial conjugated with a CCR2 antibody, its preparation method, and its application.

[0028] In a first aspect, the present invention provides a method for preparing mesoporous nanomaterials conjugated with CCR2 antibodies, comprising the following steps: Amination of mesoporous materials yields amination-modified mesoporous materials. The drug is loaded onto the aminated mesoporous material to obtain the drug-loaded aminated mesoporous material; CCR2 antibody was coupled with drug-loaded aminated mesoporous material to obtain CCR2 antibody-coupled mesoporous nanomaterial.

[0029] In this invention, an aminated mesoporous material is used to load drugs and conjugate them with a CCR2 antibody. The resulting CCR2 antibody-conjugated mesoporous nanomaterial can target CCR2+ macrophages, improving the bioavailability of drugs such as matrine and reducing side effects. This invention introduces mesoporous nanocarriers, CCR2 antibody-targeted modification, and precise macrophage delivery, forming a novel ternary combination system of carrier-drug-antibody.

[0030] In some optional embodiments, the mesoporous material is mesoporous silica, mesoporous carbon, or a mesoporous metal-organic framework. Preferably, the mesoporous material is mesoporous silica.

[0031] In some optional embodiments, the drug is matrine, rutin, rapamycin, or dexamethasone. Preferably, the drug is matrine.

[0032] In some optional embodiments, the above-mentioned amination of the mesoporous material includes: dispersing the mesoporous material in ethanol, adding 3-aminopropyltriethoxysilane, and refluxing at 70°C-90°C. Preferably, the mesoporous material is dispersed in ethanol, 3-aminopropyltriethoxysilane is added, and refluxing at 80°C.

[0033] In some alternative embodiments, loading the drug onto the aminated mesoporous material includes: dispersing the aminated mesoporous material in ethanol, adding the drug, and sonicating.

[0034] In some optional embodiments, the above-described coupling of the CCR2 antibody with the drug-loaded aminated mesoporous material includes: mixing the CCR2 antibody, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide and water, adding the drug-loaded aminated mesoporous material, and stirring the reaction.

[0035] Secondly, the present invention provides a mesoporous nanomaterial conjugated with a CCR2 antibody, which is obtained by the above-mentioned method for preparing mesoporous nanomaterial conjugated with a CCR2 antibody.

[0036] Thirdly, the present invention provides the application of the above-mentioned mesoporous nanomaterials conjugated with CCR2 antibodies in the preparation of drugs targeting CCR2+ macrophages.

[0037] Fourthly, the present invention provides a drug targeting CCR2+ macrophages, comprising the above-mentioned mesoporous nanomaterial conjugated with a CCR2 antibody.

[0038] In some optional embodiments, the aforementioned drug targeting CCR2+ macrophages is a drug for treating multi-organ damage or dysfunction caused by sepsis. Preferably, the aforementioned drug targeting CCR2+ macrophages is a drug for treating sepsis-induced lung injury, sepsis-induced myocardial injury (SIMI), or sepsis-induced kidney injury.

[0039] The following describes a typical implementation.

[0040] In the following examples, matrine (MAT), 3-aminopropyltriethoxysilane (APTES), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCl), and N-hydroxysuccinimide (NHS) were all purchased from Aladdin Biochemical Technology Co., Ltd. The CCR2 antibody was purchased from Sichuan Guotai Biotechnology Co., Ltd., and its amino acid sequence is CYNFTNRKISVQRLASYRRITSSK (SEQ ID No. 1).

[0041] Mesoporous silica (SiO2) can be obtained through the following steps: hexadecyltrimethylammonium chloride (CTAC, 0.22 g) is added to an ethanol / deionized water mixture (120 mL, ethanol:water = 11:1) and ultrasonically dispersed until completely dissolved; NaOH (39.2 mg) is added to the above system, and after stirring at 80 °C for 30 min, tetraethyl orthosilicate (TEOS, 1 mL) is added; after continuing to stir at 80 °C for 6 hours, the mixture is centrifuged and washed several times with ethanol and deionized water, and then freeze-dried to obtain SiO2 containing CTAC (CTAC@SiO2); to remove CTAC, CTAC@SiO2 (200 mg) is dispersed in methanol (100.0 mL); hydrochloric acid (37%, 10.0 mL) is added, and after reflux at 78 °C for 24 h, the mixture is centrifuged and washed several times with water, and then freeze-dried to obtain mesoporous SiO2.

[0042] Example 1 Mesoporous nanoparticles conjugated with CCR2 antibodies were prepared according to the following steps: (1) Amination of mesoporous materials Mesoporous SiO2 (0.20 g) was added to ethanol (20 mL) and sonicated until completely dispersed; then APTES (0.18 mL) was added to the dispersion and refluxed at 80 °C for 24 h; after the reaction was completed, the reactants were centrifuged and washed with water 3-4 times, and then lyophilized to obtain aminated mesoporous SiO2 (SiO2-NH2). (2) Loading the drug onto the aminated mesoporous material Aminated mesoporous SiO2 (60 mg) was added to ethanol (10 mL) and sonicated until dispersed; matrine (MAT, 30 mg) was added and sonicated again until a homogeneous mixed solution was obtained. The mixture was stirred at room temperature for 24 h to achieve sufficient loading, and centrifuged and washed to obtain matrine-loaded aminated mesoporous SiO2 (SM). (3) Coupling CCR2 antibody with drug-loaded aminated mesoporous material A mixture of CCR2 antibody (10 mg), Cy5.5 (1 mg), EDCl (0.1 mmol), and NHS (0.1 mmol) was stirred at room temperature for 1 h to activate the carboxyl groups. Then, 20 mg of SM was added, and the mixture was stirred at room temperature for 24 h. After centrifugation and washing, mesoporous silica nanoparticles (SM-PT / Cy5.5) conjugated with CCR2 antibody were obtained.

[0043] Figure 1 The TEM image of aminated mesoporous SiO2 shows that the particles exhibit a highly regular spherical structure with uniform particle size, most of which are around 50 nm in size. The high-magnification image clearly shows the porous characteristics of the particle surface. These 50 nm aminated mesoporous silica nanoparticles have unique advantages in targeted delivery applications: the surface amino groups provide active sites for subsequent coupling of targeting peptides (MCP-1 peptide), targeting ligands (CCR2 antibody), and the fluorescent dye Cy5.5, which can be formed through amide bonds (NH2 reacts with COOH); the small size facilitates passage through vascular endothelium and interstitial spaces to reach organs such as the lungs, heart, or kidneys; the mesoporous structure can efficiently load matrine; and through targeting peptide modification, precise targeting of macrophages can be achieved, improving treatment efficiency and reducing systemic toxicity.

[0044] Figure 2 and Figure 3 The images show SEM and EDS images of aminated mesoporous SiO2, respectively. The SEM image confirms the spherical structure and uniform distribution of the particles. The elemental distribution map shows the spatial distribution of Si, O and N elements. The Si and O elements have strong and uniform signals, indicating that the silica framework structure is complete. Although the N element has a weak signal, it is uniformly distributed, confirming the successful implementation of aminated functionalization.

[0045] like Figure 4As shown, the single-element distribution map and energy dispersive spectroscopy (EDS) analysis further confirmed the material composition: quantitative EDS analysis showed that the Si content was 39.13 wt% and the O content was 60.87 wt%. Notably, the N content was shown as 0.00% in the EDS table, which may be due to the N content being below the detection limit; however, a signal was still visible in the N distribution map, indicating successful amino functionalization.

[0046] Figure 5 The TEM image shows aminated mesoporous SiO2 loaded with matrine. It can be seen that the nanoparticles maintain a perfect spherical shape with a uniform diameter of approximately 50 nm, exhibiting good dispersion and no obvious agglomeration. With increasing magnification (from left to right), the unique porous network structure within each particle is clearly visible, exhibiting a typical "honeycomb" morphology. Compared to unloaded pure mesoporous silica, the drug-loaded particles show a higher electron density within the mesopores (enhanced contrast); especially in high-resolution images, a distinct grayscale deepening region is visible within the mesoporous channels, providing direct evidence of organic molecules (matrine) filling the mesoporous space. Figure 6 As shown, HAADF STEM imaging further enhanced this contrast, allowing for better differentiation between the drug-loaded area and the silicon framework, confirming that matrine successfully penetrated and distributed throughout the porous structure.

[0047] like Figure 7 As shown, the elemental mapping provides the most direct evidence of drug loading: Si and O constitute the mesoporous silica framework, while the presence of N and C elements originates from matrine molecules. Of particular note is the significant enhancement and uniform distribution of the C element signal in the particle region, indicating that matrine has successfully penetrated and is uniformly distributed throughout the mesoporous structure. Meanwhile, although the N element signal is weaker (due to the low N content in matrine molecules), its distribution closely matches the particle profile, further confirming the presence of drug loading.

[0048] like Figure 8 As shown, energy dispersive spectroscopy (EDS) further confirmed that carbon content was as high as 69.13%, and although the nitrogen content was low (0.16%), it was statistically significant (error ± 0.15%). The simultaneous presence of these two elements is consistent with the molecular composition of matrine. The atomic ratio of Si / O also deviated from the theoretical value of pure silicon dioxide due to drug loading, and this change in elemental ratio further confirms the drug loading.

[0049] Figure 9 The image shows an SEM image of aminated mesoporous SiO2 loaded with matrine. The particles maintain a spherical structure, are uniformly distributed, and have a consistent particle size of approximately 50 nm, with a regular surface morphology. Medium-magnification images further demonstrate that the nanoparticles maintain good dispersibility after drug loading, with no obvious aggregation, which is crucial for subsequent targeted delivery. Figure 10EDS images of aminated mesoporous SiO2 loaded with matrine are presented. The elemental distribution maps show the superimposed distribution of Si, O, C, and N elements, indicating uniform distribution that highly coincides with the positions of the nanoparticles. Single-element distribution maps further confirm drug loading: Si and O elements are widely distributed and show strong signals, corresponding to the silica framework; the obvious presence of C directly proves the successful loading of the organic matter (matrine); although the N element signal is weak, it is still detectable, consistent with the relatively low nitrogen content in the matrine molecule. Combining SEM morphology and EDS elemental analysis, it can be confirmed that matrine has been successfully loaded into mesoporous silica nanoparticles, and the drug loading process has not altered the basic morphological characteristics of the nanoparticles, providing a good foundation for connecting the targeting peptide and Cy5.5 fluorophore to achieve macrophage targeting.

[0050] Figure 11 The infrared spectra of aminated mesoporous SiO2, matrine-loaded aminated mesoporous SiO2, and CCR2 antibody-coupled mesoporous silica nanoparticles show that aminated mesoporous SiO2 exhibits high activity at 3400 cm⁻¹. -1 The broad peak nearby is attributed to the stretching vibrations of surface Si-OH and NH, 1630 cm⁻¹. -1 The weak absorption peak at 1090 cm⁻¹ corresponds to the bending vibration of NH₄⁺. -1 The strong absorption peak at 960 cm⁻¹ is a characteristic peak of the Si-O-Si asymmetric stretching vibration. -1 The shoulder peak at 800 cm⁻¹ represents the Si-OH stretching vibration. -1 and 460cm -1 The absorption peaks at 1630 cm⁻¹ correspond to the symmetric stretching and bending vibration modes of Si-O-Si, respectively. These characteristic peaks collectively confirm the successful synthesis of mesoporous silica and its surface amination modification. In the infrared spectrum of amination-modified mesoporous SiO₂ supported on matrine, the peak at 1630 cm⁻¹... -1 The increased intensity of the peak at 1630 cm⁻¹ is related to the C=O and C=C stretching vibrations in the matrine molecule. Meanwhile, the characteristic peaks of the silica framework (Si-O-Si vibrations) remain unchanged, indicating that the drug loading process did not alter the basic structure of the carrier. Particularly noteworthy is the peak intensity at 1630 cm⁻¹. -1 The enhancement of the peak at 1650 cm⁻¹ not only comes from the contribution of matrine, but may also reflect the hydrogen bonding between the functional groups in the matrine molecule and the amino groups on the silica surface. This interaction helps to improve the stability of drug loading. Comprehensive analysis shows that matrine has been successfully loaded into aminated mesoporous silica nanoparticles, mainly through physical adsorption and hydrogen bonding. This drug delivery system retains the basic structural features of silica while maintaining the availability of surface amino groups, providing a basis for the conjugation of targeting peptides and fluorescent labels. In the infrared spectrum of the mesoporous silica nanoparticles conjugated with CCR2 antibody, in addition to maintaining the aforementioned characteristic peaks, a peak at 1650 cm⁻¹ was observed.-1 A stronger absorption peak appeared nearby, mainly due to the C=O stretching vibration of the amide bond in the targeting peptide. Three samples showed absorption peaks at 1100 cm⁻¹. -1 Strong Si-O-Si stretching vibration peaks were observed in the vicinity, demonstrating that the integrity of the silica framework structure was maintained. Overall, the infrared spectroscopy results clearly confirmed the successful preparation process from aminated mesoporous silica to the drug-loaded composite system, and finally to the targeted fluorescent nanomedicine composite system.

[0051] Figure 12 The particle size distribution and surface charge characteristics of aminated mesoporous silica (SiO2-NH2) before and after loading with matrine were demonstrated. Particle size analysis showed that the average hydrated particle size of the silica nanoparticles before loading was 81.58 nm, exhibiting a sharp single-peak distribution, indicating uniform particle size and good dispersion. After loading with matrine, the average particle size increased to 120.0 nm, and this significant increase in particle size directly confirmed the successful loading of the drug. Simultaneously, the narrow particle size distribution and sharp peak shape were maintained after loading, indicating that the drug loading process did not lead to particle aggregation, and the system maintained a good dispersion state.

[0052] Zeta potential analysis provided crucial information on surface charge changes: before loading, the Zeta potential of aminated silica was +12.5 mV, a positive potential originating from the protonation of surface amino groups in aqueous solution; after loading matrine, the Zeta potential decreased to +7.49 mV, indicating that the matrine molecules partially shielded or neutralized the positive charge of the surface amino groups. This potential change is strong evidence of drug loading and also reflects the interaction between matrine and the carrier surface. The Zeta potential deviation decreased from 7.11 mV to 4.83 mV, indicating a more uniform surface charge distribution after loading, which may be due to the uniform distribution of the drug on the particle surface.

[0053] Based on these data, it can be confirmed that matrine has been successfully loaded into aminated mesoporous silica nanoparticles. Although the particle size has increased, the 120 nm size is still suitable for endocytosis. At the same time, the surface retains some positive charge, which not only facilitates interaction with the cell membrane, but also provides the possibility of connecting the targeting peptide and the fluorescent dye Cy5.5, which is crucial for achieving targeted delivery to macrophages.

[0054] Figure 13 The UV absorption spectra of matrine at different concentrations are presented, showing a distinct absorption peak around 200-230 nm, which is characteristic of the aromatic ring structure in the matrine molecule. The absorption peak intensity increases linearly with increasing concentration from 12.5 μg / mL to 400 μg / mL, indicating that matrine follows the Lambert-Beer law within this concentration range.

[0055] Figure 14 This is a standard curve showing the relationship between matrine concentration and absorbance. The fitted equation is y = 0.2166 + 0.00469x, with a correlation coefficient R² = 0.93, indicating a good linear relationship. This standard curve provides a quantitative basis for subsequent studies on drug loading and release kinetics.

[0056] Figure 15 The UV absorption spectra of nanoparticles before and after drug loading were compared: the absorption of the SM sample (after drug loading) in the 200-230 nm range was significantly higher than that of SiO2-NH2 (before drug loading), which perfectly matches the characteristic absorption peak of matrine, directly proving the successful loading of matrine. Simultaneously, a new absorption peak appeared in the SM sample near 250 nm, which may be due to contributions from other chromophores in the matrine molecule, or a spectral shift caused by the interaction between matrine and functional groups on the silica surface. Substituting the intensity of this absorption peak into the matrine drug standard curve equation, the drug loading amount could be finally calculated to be 5.25%.

[0057] The above description is merely a preferred embodiment of the present invention. The present invention is not limited to the above-described embodiments. Any embodiment that achieves the technical effects of the present invention by the same or equivalent means should fall within the protection scope of the present invention. Within the protection scope of the present invention, various modifications and variations can be made to the technical solutions and / or implementation methods.

Claims

1. A method for preparing mesoporous nanomaterials conjugated with CCR2 antibodies, characterized in that, Includes the following steps: Amination of mesoporous materials yields amination-modified mesoporous materials. The drug is loaded onto the aminated mesoporous material to obtain the drug-loaded aminated mesoporous material; CCR2 antibody was coupled with drug-loaded aminated mesoporous material to obtain CCR2 antibody-coupled mesoporous nanomaterial.

2. The method according to claim 1, characterized in that, The mesoporous material is mesoporous silica, mesoporous carbon, or mesoporous metal-organic framework.

3. The method according to claim 1, characterized in that, The drug is matrine, rutin, rapamycin, or dexamethasone.

4. The method according to claim 1, characterized in that, The process of amination of the mesoporous material includes: dispersing the mesoporous material in ethanol, adding 3-aminopropyltriethoxysilane, and refluxing at 70°C-90°C.

5. The method according to claim 1, characterized in that, The process of loading the drug onto the aminated mesoporous material includes: dispersing the aminated mesoporous material in ethanol, adding the drug, and ultrasonic treatment.

6. The method according to claim 1, characterized in that, The coupling of CCR2 antibody with drug-loaded aminated mesoporous material includes: mixing CCR2 antibody, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride, N-hydroxysuccinimide and water, adding drug-loaded aminated mesoporous material, and stirring to react.

7. A mesoporous nanomaterial conjugated with a CCR2 antibody, characterized in that, It is obtained by the preparation method of the mesoporous nanomaterial conjugated with CCR2 antibody according to any one of claims 1-6.

8. The application of the mesoporous nanomaterial conjugated with CCR2 antibody according to claim 7 in the preparation of drugs targeting CCR2+ macrophages.

9. A drug targeting CCR2+ macrophages, comprising the mesoporous nanomaterial conjugated with the CCR2 antibody as described in claim 7.

10. The drug targeting CCR2+ macrophages according to claim 9, characterized in that, The drug targeting CCR2+ macrophages is used to treat multi-organ damage or dysfunction caused by sepsis.

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