Nanomaterials for delivering udp-glcNAc and methods of making and using the same

Abstract

The application relates to the technical field of medicines, in particular to a kind of nanometer material for delivering UDP-GlcNAc and its preparation method and application.The application provides a kind of nanometer material for delivering UDP-GlcNAc, the nanometer material is prepared by co-precipitation method from metal ion and uridine diphosphate-N-acetylglucosamine;Wherein, the metal ion includes magnesium ion, calcium ion, iron ion, zinc ion, aluminum ion, copper ion, manganese ion, cobalt ion, nickel ion and chromium ion in any one of them.The efficient intracellular delivery is realized, and the drug action time is prolonged, which is beneficial to wide application.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical technology, and in particular relates to a nanomaterial for delivering UDP-GlcNAc, its preparation method and application. Background Technology

[0002] AMPK (AMP-activated protein kinase), as a core regulatory molecule of cellular energy metabolism, plays a crucial role in maintaining energy homeostasis in the body. Activation of AMPK can promote fatty acid oxidation, inhibit fat synthesis, and improve mitochondrial function, thus it is considered an important drug target for treating metabolic diseases (such as fatty liver and type 2 diabetes) and delaying aging.

[0003] Despite the unique advantages UDP-GlcNAc exhibits in AMPK activation, its practical application is severely limited by pharmacokinetic factors. First, as a highly polar hydrophilic molecule, UDP-GlcNAc struggles to penetrate the lipid bilayer of cell membranes via passive diffusion, resulting in extremely low bioavailability. Second, even when introduced into cells under experimental conditions using specialized methods, UDP-GlcNAc's intracellular retention time is extremely short, making it readily metabolized or excreted. This leads to a "pulsating" effect in AMPK activation, failing to maintain sustained therapeutic concentrations. This makes long-term in vivo intervention using UDP-GlcNAc for chronic diseases such as fatty liver and diabetes virtually impossible, significantly limiting the clinical application potential of this natural metabolite.

[0004] Therefore, there is an urgent need to provide a new method to enable UDP-GlcNAc to effectively enter cells and how to effectively and continuously exert its effects within cells. Summary of the Invention

[0005] The purpose of this application is to provide a nanomaterial for delivering UDP-GlcNAc, its preparation method and application, aiming to solve the problem that there is no effective way to deliver UDP-GlcNAc into cells in the prior art.

[0006] To achieve the above-mentioned objectives, the technical solution adopted in this application is as follows: In a first aspect, this application provides a nanomaterial for delivering UDP-GlcNAc, wherein the nanomaterial is prepared by co-precipitation of metal ions with uridine diphosphate-N-acetylglucosamine; wherein the metal ions include any one of magnesium ions, calcium ions, iron ions, zinc ions, aluminum ions, copper ions, manganese ions, cobalt ions, nickel ions and chromium ions.

[0007] In some embodiments, the preparation method of nanomaterials includes the following steps: mixing a salt solution containing metal ions with an aqueous solution of UDP-GlcNAc at room temperature, adding an alkaline solution to adjust the pH value of the solution and then continuing to mix, collecting the precipitate to obtain nanomaterials.

[0008] In some embodiments, the molar ratio of the salt solution containing metal ions to the aqueous solution of UDP-GlcNAc is (1.5-2.5):1.

[0009] In some embodiments, the concentration of the salt solution containing metal ions is 15-25 mM.

[0010] In some embodiments, the concentration of the UDP-GlcNAc aqueous solution is 8~12 mM.

[0011] In some embodiments, the mixing process takes 40 minutes to 3 hours.

[0012] In some embodiments, in the step of adding an alkaline solution to adjust the pH of the solution, the alkaline solution includes a sodium hydroxide solution, and the pH is adjusted to 9-11.

[0013] Secondly, this application provides the use of nanomaterials that deliver UDP-GlcNAc in the preparation of drugs for activating the intracellular AMPK signaling pathway.

[0014] Thirdly, this application provides the use of nanomaterials delivering UDP-GlcNAc in the preparation of medicaments for the treatment of non-alcoholic fatty liver disease.

[0015] Fourthly, this application provides the use of nanomaterials delivering UDP-GlcNAc in the preparation of medicaments for treating acute liver injury.

[0016] In some embodiments, after the nanomaterials enter the cells, they reduce the intracellular fat content by downregulating the expression of lipogenesis-related genes srebp1c and Fasn, and upregulating the expression of lipolysis-related genes atgl and hsl.

[0017] The first aspect of this application provides a nanomaterial for delivering UDP-GlcNAc, wherein the nanomaterial is prepared by co-precipitation of metal ions with uridine diphosphate-N-acetylglucosamine; wherein the metal ions include any one of magnesium ions, calcium ions, iron ions, zinc ions, aluminum ions, copper ions, manganese ions, cobalt ions, nickel ions and chromium ions. First, by utilizing the coordination of functional groups such as phosphate groups in the UDP-GlcNAc molecule with metal ions, nanoscale particles are formed through self-assembly. By assembling UDP-GlcNAc into the nanostructure, its active groups can be effectively masked, significantly improving its stability in the physiological environment, preventing its rapid degradation by free enzymes, and prolonging its circulation time in vivo. Second, the nanomaterial can be taken up by cells through endocytosis and other pathways, solving the problem of poor cell membrane permeability of free UDP-GlcNAc and achieving efficient intracellular delivery. Finally, this nanomaterial consists only of metal ions and the active drug component UDP-GlcNAc, avoiding the biocompatibility risks that may arise from using polymeric carriers. The preparation process is simple and environmentally friendly. Furthermore, by selecting different types of metal ions, the particle size, surface charge, and drug release behavior of the nanomaterial can be adjusted, providing ample room for subsequent material optimization for different therapeutic needs.

[0018] The application of the nanomaterial for delivering UDP-GlcNAc provided in the second aspect of this application in the preparation of drugs for activating the intracellular AMPK signaling pathway; after being taken up by cells, the nanomaterial can achieve slow release of UDP-GlcNAc within the cells, and the sustained release mediated by the nanomaterial can prolong the activation time of AMPK. This sustained activation effect has profound pharmacological significance for restoring energy metabolism homeostasis, inhibiting anabolism, and promoting catabolism, and provides the possibility for developing novel therapies for metabolic syndrome.

[0019] The nanomaterial for delivering UDP-GlcNAc provided in the third aspect of this application is used in the preparation of drugs for treating non-alcoholic fatty liver disease. The UDP-GlcNAc delivered by the nanomaterial efficiently can strongly inhibit fat synthesis in the liver and promote fatty acid oxidation by prolonging the activation time of AMPK, thereby reducing lipid accumulation in hepatocytes and providing a key means for treating non-alcoholic fatty liver disease.

[0020] In the application of the nanomaterials for delivering UDP-GlcNAc provided in the fourth aspect of this application in the preparation of drugs for treating acute liver injury, UDP-GlcNAc, as a precursor-1 for the synthesis of glycosaminoglycans (such as hyaluronic acid), may play a protective role against acute liver injury by maintaining extracellular matrix homeostasis and enhancing the resistance of hepatocytes to damaging factors. Simultaneously, the passive targeting characteristic of the nanomaterials to the liver allows for drug accumulation in the liver, improving therapeutic efficacy and reducing potential systemic side effects. Therefore, nanomaterials for delivering UDP-GlcNAc provide a key approach for treating acute liver injury. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of this application, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is the morphological and structural characterization analysis result of MgUGN provided in Example 1 of this application; Figure 2 This is the experimental analysis result provided in Example 1 of this application, showing that MgUGN can enter cells and prolong the activation time of AMPK; Figure 3 This is the experimental analysis result of MgUGN, as provided in Example 1 of this application, being able to reduce intracellular lipid content; Figure 4 This is the experimental analysis result of MgUGN treatment for fatty liver and acute liver injury provided in Example 1 of this application. Detailed Implementation

[0023] To make the technical problems, technical solutions, and beneficial effects of this application clearer, the following detailed description is provided in conjunction with embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the scope of this application.

[0024] In this application, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. A and B can be singular or plural. The character " / " generally indicates that the preceding and following related objects have an "or" relationship.

[0025] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single or multiple items. For example, "at least one of a, b, or c", or "at least one of a, b, and c", can both mean: a, b, c, ab (i.e., a and b), ac, bc, or abc, where a, b, and c can be single or multiple.

[0026] It should be understood that in the various embodiments of this application, the order of the above processes does not imply the order of execution. Some or all steps may be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application.

[0027] The terminology used in the embodiments of this application is for the purpose of describing particular embodiments only and is not intended to be limiting of this application. The singular forms "a" and "the" as used in the embodiments of this application and the appended claims are also intended to include the plural forms, unless the context clearly indicates otherwise.

[0028] The weights of the relevant components mentioned in the embodiments of this application can refer not only to the specific content of each component, but also to the proportional relationship between the weights of the components. Therefore, any scaling up or down of the content of the relevant components according to the embodiments of this application is within the scope disclosed in the embodiments of this application. Specifically, the mass in the embodiments of this application can be a well-known unit of mass in the chemical industry, such as µg, mg, g, or kg.

[0029] The terms "first" and "second" are used for descriptive purposes only, to distinguish objects, such as substances, from one another, and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features indicated. For example, without departing from the scope of the embodiments of this application, "first XX" may also be referred to as "second XX," and similarly, "second XX" may also be referred to as "first XX." Thus, features defined with "first" and "second" may explicitly or implicitly include one or more of that feature.

[0030] The first aspect of this application provides a nanomaterial for delivering UDP-GlcNAc. The nanomaterial is prepared by co-precipitation of metal ions and uridine diphosphate-N-acetylglucosamine. The metal ions include any one of magnesium ions, calcium ions, iron ions, zinc ions, aluminum ions, copper ions, manganese ions, cobalt ions, nickel ions, and chromium ions.

[0031] The first aspect of this application provides a nanomaterial for delivering UDP-GlcNAc. The nanomaterial is prepared by co-precipitation of metal ions with uridine diphosphate-N-acetylglucosamine. The metal ions include any one of magnesium ions, calcium ions, iron ions, zinc ions, aluminum ions, copper ions, manganese ions, cobalt ions, nickel ions, and chromium ions. First, by utilizing the coordination of functional groups such as phosphate groups in the UDP-GlcNAc molecule with metal ions, nanoscale particles are formed through self-assembly. By assembling UDP-GlcNAc into the nanostructure, its active groups can be effectively masked, significantly improving its stability in the physiological environment, preventing its rapid degradation by free enzymes, and prolonging its circulation time in vivo. Second, the nanomaterial can be taken up by cells through endocytosis and other pathways, solving the problem of poor cell membrane permeability of free UDP-GlcNAc and achieving efficient intracellular delivery. Finally, this nanomaterial consists only of metal ions and the active drug component UDP-GlcNAc, avoiding the biocompatibility risks that may arise from using polymeric carriers. The preparation process is simple and environmentally friendly. Furthermore, by selecting different types of metal ions, the particle size, surface charge, and drug release behavior of the nanomaterial can be adjusted, providing ample room for subsequent material optimization for different therapeutic needs.

[0032] In some embodiments, the preparation method of nanomaterials includes the following steps: mixing a salt solution containing metal ions with an aqueous solution of UDP-GlcNAc at room temperature, adding an alkaline solution to adjust the pH value of the solution and then continuing to mix, collecting the precipitate to obtain nanomaterials.

[0033] This preparation method is carried out entirely at room temperature, avoiding the damage of heat-sensitive biomolecules like UDP-GlcNAc to high temperatures and maximizing the protection of its structural integrity and bioactivity. Secondly, the "co-precipitation method" employing mixing followed by pH adjustment is simple, mild, and easy to scale up for production, avoiding the use of organic solvents and meeting the requirements of green chemistry. Finally, by adjusting the pH value, the hydrolysis rate of metal ions and their coordination assembly with UDP-GlcNAc can be precisely controlled, thereby achieving regulation of nanomaterial nucleation and growth, ensuring the formation of uniformly sized and structurally stable nanoparticles. This mild and efficient preparation method forms the technological basis for ensuring the excellent delivery performance and stability of the final nanomaterials.

[0034] In some embodiments, the molar ratio of the salt solution containing metal ions to the aqueous solution of UDP-GlcNAc is (1.5-2.5):1.

[0035] The molar ratio of the salt solution containing metal ions to the aqueous solution of UDP-GlcNAc was limited to (1.5-2.5):1. At this molar ratio, the metal ions can fully coordinate with the phosphate groups and hydroxyl groups in the UDP-GlcNAc molecule to form a dense and stable network nanostructure, while avoiding rapid flocculation or precipitation caused by excessive metal ions. Experiments have shown that within this preferred range, the prepared nanomaterials exhibit a narrower particle size distribution (low polydispersity index), higher drug encapsulation efficiency and drug loading, and better colloidal stability in solution. This facilitates the uniformity and reproducibility of the quality of each batch of nanomaterials, laying a solid material foundation for their subsequent biological evaluation and clinical application.

[0036] In some specific embodiments, the molar ratio of the salt solution containing metal ions to the aqueous solution of UDP-GlcNAc is a typical but non-limiting value such as 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2.0:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1.

[0037] In some embodiments, the concentration of the salt solution containing metal ions is 15-25 mM.

[0038] In some embodiments, the concentration of the UDP-GlcNAc aqueous solution is 8~12 mM.

[0039] The concentration of the salt solution containing metal ions was limited to 15–25 mM, and the concentration of the UDP-GlcNAc aqueous solution was limited to 8–12 mM. By controlling the concentrations of the two reactants within the above-mentioned preferred ranges, a stable and controllable supersaturated environment can be created, allowing the co-precipitation reaction to generate a large number of uniform crystal nuclei instantaneously. Subsequently, the crystal nuclei grow synchronously, ultimately yielding nanomaterials with uniform particle size and good dispersibility. This concentration range also takes into account production efficiency, enabling a considerable product yield while ensuring product quality, and providing a key process parameter window for the transformation from laboratory research to large-scale production.

[0040] In some specific embodiments, the concentration of the salt solution containing metal ions includes, but is not limited to, typical but non-limiting values ​​such as 15 mM, 16 mM, 17 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, and 25 mM.

[0041] In some specific embodiments, the concentration of the UDP-GlcNAc aqueous solution includes, but is not limited to, typical but non-limiting values ​​such as 8 mM, 9 mM, 10 mM, 11 mM, and 12 mM.

[0042] In some embodiments, the mixing process takes 40 minutes to 3 hours. The mixing process includes a first mixing process lasting 40-50 minutes; and a second mixing process lasting 2-3 hours after the addition of the alkali solution.

[0043] The mixing process primarily involves the formation of crystal nuclei during the initial mixing phase (approximately 40 minutes). Adding alkali to adjust the pH of the solution followed by continuous mixing for up to 3 hours helps reduce the surface energy of the newly formed nanoparticles, leading to a more regular and stable crystal structure and improved colloidal stability. If the initial mixing phase is less than 40 minutes, the resulting material may be amorphous or poorly loaded with drug, potentially causing a drug burst. If mixing continues for more than 3 hours, the nanoparticles may aggregate and precipitate due to continuous collisions.

[0044] In some embodiments, in the step of adding an alkaline solution to adjust the pH of the solution, the alkaline solution includes a sodium hydroxide solution, and the pH is adjusted to 9-11.

[0045] Under these pH conditions, most divalent or trivalent metal ions can undergo moderate hydrolysis to form polynuclear hydroxy-bridged complexes with coordination activity, while ensuring that the phosphate groups in the UDP-GlcNAc molecule are negatively charged. This allows for self-assembly into ordered, uniformly sized nanomaterials through electrostatic attraction and the synergistic effect of coordination bonds. The weakly alkaline environment of pH 9-11 avoids the destruction of UDP-GlcNAc glycosidic bonds by strong alkaline conditions, while also ensuring that the nanomaterials possess suitable surface charges, which is beneficial for their stable dispersion in aqueous media and prevents aggregation.

[0046] The second aspect of this application provides the use of nanomaterials that deliver UDP-GlcNAc in the preparation of drugs for activating the intracellular AMPK signaling pathway.

[0047] The application of the nanomaterial for delivering UDP-GlcNAc provided in the second aspect of this application in the preparation of a drug for activating the intracellular AMPK signaling pathway; after being taken up by cells, the nanomaterial can achieve slow release of UDP-GlcNAc within the cells, and the sustained release mediated by the nanomaterial can prolong the activation time of AMPK. This sustained activation effect has profound pharmacological significance for restoring energy metabolism homeostasis, inhibiting anabolism, and promoting catabolism, and provides the possibility for developing novel therapies for metabolic syndrome.

[0048] The third aspect of this application provides the use of nanomaterials delivering UDP-GlcNAc in the preparation of medicaments for treating non-alcoholic fatty liver disease.

[0049] The nanomaterial for delivering UDP-GlcNAc provided in the third aspect of this application is used in the preparation of a drug for treating non-alcoholic fatty liver disease. The UDP-GlcNAc delivered by the nanomaterial efficiently prolongs the activation time of AMPK, which can strongly inhibit fat synthesis in the liver and promote fatty acid oxidation, thereby reducing lipid accumulation in hepatocytes and providing a key means for treating non-alcoholic fatty liver disease.

[0050] The fourth aspect of this application provides the use of nanomaterials delivering UDP-GlcNAc in the preparation of medicaments for treating acute liver injury.

[0051] In the application of the nanomaterials for delivering UDP-GlcNAc provided in the fourth aspect of this application in the preparation of drugs for treating acute liver injury, UDP-GlcNAc, as a precursor for the synthesis of glycosaminoglycans (such as hyaluronic acid), may play a protective role against acute liver injury by maintaining the homeostasis of the extracellular matrix of hepatocytes and enhancing the resistance of hepatocytes to damaging factors. Simultaneously, the passive targeting characteristic of the nanomaterials to the liver allows the drug to accumulate in the liver, improving therapeutic efficacy and reducing potential systemic side effects. Therefore, nanomaterials for delivering UDP-GlcNAc provide a key means for treating acute liver injury.

[0052] In some embodiments, after the nanomaterials enter the cells, they reduce the intracellular fat content by downregulating the expression of lipogenesis-related genes srebp1c and Fasn, and upregulating the expression of lipolysis-related genes atgl and hsl.

[0053] The following description is based on specific embodiments.

[0054] Example 1 MgUGN nanoparticles and their preparation methods The preparation method is as follows: Under continuous stirring at room temperature, 5 mL of MgCl2 aqueous solution (concentration 20 mM) was slowly added to 5 mL of UDP-GlcNAc aqueous solution (concentration 10 mM). After stirring for 30 min, 40 μL of 5 M NaOH aqueous solution was added to the system, forming a pale white precipitate. After the reaction continued for 2 h, the precipitate was collected by centrifugation at 12000 rpm for 5 min, washed three times with deionized water, and finally freeze-dried to obtain MgUGN nanoparticles.

[0055] Example 2 CaUGN nanoparticles and their preparation methods Compared with Example 1, the "MgCl2 aqueous solution" was replaced with "CaCl2 aqueous solution"; all other conditions were the same, and CaUGN nanoparticles were finally obtained.

[0056] Example 3 FeUGN nanoparticles and their preparation methods Compared with Example 1, the "MgCl2 aqueous solution" was replaced with "FeCl2 aqueous solution"; all other conditions were the same, and FeUGN nanoparticles were finally obtained.

[0057] Example 4 ZnUGN nanoparticles and their preparation methods Compared with Example 1, the "MgCl2 aqueous solution" was replaced with "ZnCl2 aqueous solution"; all other conditions were the same, and ZnUGN nanoparticles were finally obtained.

[0058] Example 5 CuUGN nanoparticles and their preparation methods Compared with Example 1, the "MgCl2 aqueous solution" was replaced with "CuCl2 aqueous solution"; all other conditions were the same, and CuUGN nanoparticles were finally obtained.

[0059] Example 6 MnUGN nanoparticles and their preparation methods Compared with Example 1, the "MgCl2 aqueous solution" was replaced with "MnCl2 aqueous solution"; all other conditions were the same, and MnUGN nanoparticles were finally obtained.

[0060] Example 7 NiUGN nanoparticles and their preparation methods Compared with Example 1, the "MgCl2 aqueous solution" was replaced with "NiCl2 aqueous solution"; all other conditions were the same, and NiUGN nanoparticles were finally obtained.

[0061] Comparative Example 1 UGN is provided directly.

[0062] Performance Testing and Result Analysis Taking the MgUGN prepared in Example 1 as an example, the following analysis and explanation are provided.

[0063] 1. For example Figure 1 A and Figure 1 As shown in Figure B, the prepared MgUGN exhibits a small-sized, nanosheet-like morphology. Elemental distribution diagram ( Figure 1 The C-ray diffraction (C) results show that Mg, P, C, N, and O elements are uniformly distributed within the nanosheets. The presence of P, an inherent component of the UDP-GlcNAc molecule, indicates successful coordination of UDP-GlcNAc with magnesium ions, thus forming a stable nanosheet structure. Dynamic light scattering (DLS) measurements show that the hydrodynamic diameter of the MgUGN nanosheets is 338.47 ± 21.58 nm. Figure 1The weakly alkaline reaction environment promoted the formation of Mg(OH)2, and X-ray diffraction (XRD) analysis confirmed that the crystal phase of the MgUGN nanosheets corresponded to that of Mg(OH)2. Figure 1 E). 2. MgUGN can enter cells and prolong the activation time of AMPK. like Figure 2 A and Figure 2 As shown in Figure B, directly adding UDP-GlcNAc to the cell culture medium cannot activate AMPK, but transfecting UDP-GlcNAc into cells via electroporation can temporarily activate AMPK, from 1 to 2 hours. Figure 2 C and Figure 2 (D). Considering its inability to enter cells and its short activation time, UDP-GlcNAc, even if it could activate AMPK, would not produce any metabolic changes. MgUGN, on the other hand, can enter cells directly upon addition to the culture medium. Figure 2 Other metal ion-based nanomaterials can also enter cells, but MgUGN composed of Mg ions is the most effective, activating from 1 hour to 36 hours. Figure 2 The FG showed better cell permeability and significantly better AMPK sustained activation ability than UDP-GlcNAc.

[0064] 3. MgUGN can reduce intracellular fat content. UDP-GlcNAc was added to cells via electroporation, and MgUGN was added directly to the cell culture medium. Cells were harvested and analyzed after 48 hours. It was found that UDP-GlcNAc could activate AMPK, but it could not alter the expression levels of downstream lipid metabolism genes such as atgl, hsl, srebp1c, and Fasn. Figure 3 MgUGN upregulated the lipid degradation genes atgl and hsl, and downregulated the lipid synthesis genes srebp1c and Fasn. Simultaneously, the lipid metabolites triglycerides and acyl-CoA were also reduced, indicating that lipid metabolism was indeed decreased. Figure 3 The BC). UDP-GlcNAc remained unchanged. Finally, it can be seen that the addition of MgUGN reduces the number of lipid droplets representing overall fat content, while UDP-GlcNAc remains unchanged ( ). Figure 3 (DE). These results indicate that MgUGN can reduce intracellular lipid content by activating AMPK for a prolonged period.

[0065] 4. MgUGN can treat non-alcoholic fatty liver disease and acute liver injury. MgUGN was injected via tail vein into ob / ob mice, a common animal model of fatty liver, at a dose of 10 mg / kg every three days for two weeks. After two weeks, the mice were sacrificed, and liver tissue was harvested to detect p-AMPK levels. Oil Red O staining was used to assess liver fat levels. The results showed that MgUGN significantly activated AMPK in the liver (…). Figure 4 A- Figure 4 (B), and significantly reduced the fat content in the liver ( Figure 4 The results indicate that MgUGN can treat fatty liver by activating AMPK in the liver. Additionally, we induced an acute liver injury model by intravenous injection of APAP (250 mg / kg) 24 hours prior to modeling, and observed a protective effect against acute liver injury by adding MgUGN 2 hours before APAP (acetaminophen). The results show that MgUGN can effectively prevent APAP-induced acute liver injury (C). Figure 4 D- Figure 4 The E value indicates the potential of MgUGN in the treatment of acute liver injury.

[0066] This application provides a nanomaterial for delivering UDP-GlcNAc. The nanomaterial is prepared by co-precipitation of metal ions with uridine diphosphate-N-acetylglucosamine. The metal ions include magnesium ions, calcium ions, iron ions, zinc ions, aluminum ions, copper ions, manganese ions, cobalt ions, nickel ions, and chromium ions. First, by utilizing the coordination of functional groups such as phosphate groups in the UDP-GlcNAc molecule with metal ions, nanoscale particles are formed through self-assembly. By assembling UDP-GlcNAc into the nanostructure, its active groups can be effectively masked, significantly improving its stability in the physiological environment, preventing its rapid degradation by free enzymes, and prolonging its circulation time in vivo. Second, the nanomaterial can be taken up by cells through endocytosis and other pathways, solving the problem of poor cell membrane permeability of free UDP-GlcNAc and achieving efficient intracellular delivery. Finally, this nanomaterial consists only of metal ions and the active drug component UDP-GlcNAc, avoiding the biocompatibility risks that may arise from using polymeric carriers. The preparation process is simple and environmentally friendly. Furthermore, by selecting different types of metal ions, the particle size, surface charge, and drug release behavior of the nanomaterial can be adjusted, providing ample room for subsequent material optimization for different therapeutic needs.

[0067] The above description is merely a preferred embodiment of this application and is not intended to limit this application. Any modifications, equivalent substitutions, and improvements made within the spirit and principles of this application should be included within the protection scope of this application.

Claims

1. A nanomaterial for delivering UDP-GlcNAc, characterized in that, The nanomaterial is prepared by co-precipitation of metal ions and uridine diphosphate-N-acetylglucosamine; wherein the metal ions include any one of magnesium ions, calcium ions, iron ions, zinc ions, aluminum ions, copper ions, manganese ions, cobalt ions, nickel ions and chromium ions.

2. The nanomaterial according to claim 1, characterized in that, The preparation method of the nanomaterial includes the following steps: mixing a salt solution containing metal ions with an aqueous solution of UDP-GlcNAc at room temperature, adding an alkaline solution to adjust the pH value of the solution and then continuing to mix, collecting the precipitate to obtain the nanomaterial.

3. The nanomaterial according to claim 2, characterized in that, The molar ratio of the salt solution containing metal ions to the aqueous solution of UDP-GlcNAc is (1.5-2.5):

1.

4. The nanomaterial according to claim 2, characterized in that, The concentration of the salt solution containing metal ions is 15-25 mM; and / or, The concentration of the UDP-GlcNAc aqueous solution is 8~12 mM.

5. The nanomaterial according to claim 2, characterized in that, The mixing process takes 40 minutes to 3 hours.

6. The nanomaterial according to claim 2, characterized in that, In the step of adding an alkaline solution to adjust the pH of the solution, the alkaline solution includes a sodium hydroxide solution and is adjusted to a pH of 9-11.

7. The use of the nanomaterial for delivering UDP-GlcNAc according to any one of claims 1 to 6 in the preparation of a drug for activating the intracellular AMPK signaling pathway.

8. The use of the nanomaterial for delivering UDP-GlcNAc according to any one of claims 1 to 6 in the preparation of a medicament for treating non-alcoholic fatty liver disease and / or acute liver injury.

9. The use of the nanomaterial for delivering UDP-GlcNAc according to any one of claims 1 to 6 in the preparation of a medicament for treating acute liver injury.

10. The application according to claim 7, characterized in that, After entering the cells, the nanomaterials reduce intracellular fat content by downregulating the expression of lipid synthesis-related genes srebp1c and Fasn, and upregulating the expression of lipid breakdown-related genes atgl and hsl.

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