Preparation method and application of resveratrol loaded europium doped layered double hydroxide nanomaterial

Abstract

This invention relates to the field of nanobiomedicine, and discloses a method for preparing resveratrol-loaded europium-doped layered double hydroxide nanomaterials and their applications. First, using LDH as a base nanocarrier, europium ions are introduced to dope the LDH layered structure, forming Eu-LDH nanomaterials. LDH consists of positively charged metal hydroxide layers with tunable interlayer spaces. Utilizing the layered structure, bioactive resveratrol molecules can be stably loaded into the interlayer structure through intercalation or adsorption, thereby forming an REu-LDH nanocomposite system. This structure improves the stability and bioavailability of resveratrol while achieving slow drug release. The resulting nanomaterials can be used to prepare drugs to alleviate radiation-induced lung injury, reducing radiation-induced oxidative stress damage, inhibiting the release of inflammatory factors and regulating immune responses, and delaying or inhibiting the progression of pulmonary fibrosis.

Description

Technical Field

[0001] This invention relates to the field of nanobiomedicine technology, and more specifically to a method for preparing and applying resveratrol-supported europium-doped layered double hydroxide nanomaterials. Background Technology

[0002] Radiation-induced lung injury (RILI) is a common and dose-limiting complication during radiotherapy for thoracic tumors. Its development is closely related to multiple factors, including oxidative stress, persistent inflammatory response, and immune imbalance. Ionizing radiation can induce the generation of large amounts of reactive oxygen species (ROS), leading to pathological changes such as alveolar epithelial cell damage, inflammatory cell infiltration, and fibrotic remodeling. Current clinical treatment mainly relies on anti-inflammatory drugs such as glucocorticoids, but this approach has several limitations, including:

[0003] 1. Limited treatment options: Currently, anti-inflammatory drugs mainly focus on the inflammatory stage, with limited effect on inhibiting the progression of fibrosis in the later stages, and long-term use may produce significant side effects.

[0004] 2. Insufficient antioxidant capacity: During radiation damage, a large amount of ROS is generated, and traditional drugs are unable to effectively remove the continuously generated free radicals.

[0005] 3. Poor drug stability and targeting: Natural antioxidant molecules such as resveratrol have good biological activity, but they have poor water solubility, rapid metabolism in vivo, and low bioavailability.

[0006] 4. Lack of multi-mechanism synergistic treatment strategies: The occurrence of RILI involves multiple links such as oxidative stress, inflammatory response and fibrosis, and it is difficult for a single drug to regulate multiple pathological processes at the same time.

[0007] Therefore, developing multi-target therapeutic strategies that can simultaneously regulate oxidative stress and inflammatory responses is of great significance. In recent years, nanomedicine delivery systems have attracted widespread attention in the field of radiation injury treatment due to their controllable structure and good drug loading capacity. Among them, layered double hydroxides (LDHs) are a class of inorganic nanomaterials with a two-dimensional layered structure, exhibiting high drug loading capacity and good biocompatibility. Furthermore, resveratrol (RES), a natural polyphenol compound, possesses various biological functions such as antioxidant, anti-inflammatory, and anti-fibrotic effects; however, its poor water solubility and low bioavailability limit its clinical application.

[0008] Therefore, how to provide a method for preparing and applying resveratrol-supported europium-doped layered double hydroxide nanomaterials is a problem that urgently needs to be solved by those skilled in the art. Summary of the Invention

[0009] In view of this, the present invention provides a method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials and their applications. The obtained nanomaterials can be used to prepare drugs to alleviate radiation-induced lung injury, reduce radiation-induced oxidative stress damage, inhibit the release of inflammatory factors and regulate immune responses, and delay or inhibit the progression of pulmonary fibrosis.

[0010] To achieve the above objectives, the present invention adopts the following technical solution: A method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials includes the following steps: (1) First, dissolve Co(NO3)2·6H2O, Al(NO3)3·9H2O and EuCl3·6H2O in deionized water to obtain solution A; dissolve NaOH and Na2CO3 in deionized water to obtain solution B; (2) Under nitrogen protection and magnetic stirring conditions, solution A and solution B were simultaneously added dropwise to the reaction system, and the pH of the system was maintained. After the addition was completed, the reaction mixture was transferred to the reaction vessel for hydrothermal reaction. After the reaction was completed, the precipitate was washed to neutral and lyophilized to obtain Eu-LDH powder. (3) Dissolve resveratrol in ethanol, add Eu-LDH dispersion, and stir magnetically under light-protected conditions to load resveratrol into the LDH interlayer structure; after the reaction is completed, centrifuge to remove unbound resveratrol, wash 2-3 times and freeze dry to obtain the final product.

[0011] The unique electronic structure and tunable redox properties of rare earth elements offer potential advantages in regulating the antioxidant activity and biological response of materials. This invention, by introducing europium into the LDH lattice, enhances its functional performance while retaining its loading and delivery advantages, thereby improving its ability to regulate oxidative stress. However, Eu-LDH primarily functions through non-specific free radical scavenging, with limited ability to directly influence key inflammatory and immune pathways associated with radiation-induced lung injury. This limitation highlights the need to develop a multifunctional nanoplatform capable of simultaneously modulating oxidative stress, inflammatory signaling, and immune homeostasis. This invention utilizes these properties to prepare an organic-inorganic hybrid nanocomposite material through the self-assembly of RES and Eu-LDH. Within this framework, RES provides excellent free radical scavenging capabilities and modulates the Nrf2 and NF-κB pathways, while Eu-LDH possesses natural ROS-trapping capabilities and stabilizes RES into a two-dimensional nanoscale scaffold. Eu-LDH can simultaneously scavenge ROS and inhibit inflammatory responses, thereby reducing oxidative stress levels and alleviating lung tissue damage.

[0012] First, using LDH as a basic nanocarrier, europium ions were introduced to dope the LDH lamellar structure, forming Eu-LDH nanomaterials. LDH consists of positively charged metal hydroxide lamellars with tunable interlayer spaces. Utilizing this layered structure, bioactive resveratrol molecules can be stably loaded into the interlayer structure via intercalation or adsorption, thus forming an REu-LDH nanocomposite system. This structure improves the stability and bioavailability of resveratrol while achieving slow drug release.

[0013] Preferably, in step (1), Co 2+ :(Al 3+ +Eu 3+ The molar ratio of Al is 3:1; 3+ Eu 3+ The molar ratio is 1:0.2.

[0014] Preferably, in step (1), the molar ratio of NaOH to Na2CO3 is 4:1.

[0015] Preferably, in step (2), the pH of the maintenance system is 10.0 ± 0.02.

[0016] Preferably, in step (2), the temperature of the hydrothermal reaction is 130°C and the time is 10 h.

[0017] Preferably, in step (3), the mass ratio of resveratrol to Eu-LDH powder is 1:1.

[0018] Preferably, in step (3), the magnetic stirring time is 24 h.

[0019] The present invention also provides nanomaterials obtained by the above preparation method.

[0020] The present invention also provides the application of the above-mentioned nanomaterials in the preparation of drugs to alleviate radiation-induced lung injury.

[0021] Compared with existing technologies, this invention synthesizes europium-doped layered double hydroxide nanomaterials via a co-precipitation method, loading resveratrol into the LDH layered structure to form REu-LDH nanocomposite materials. The combination of resveratrol and Eu-LDH enhances the material's ability to scavenge reactive oxygen species and its anti-inflammatory properties. REu-LDH exerts a synergistic therapeutic effect through multiple mechanisms, including ROS scavenging, inhibition of inflammatory signaling pathways, and regulation of immune responses. Attached Figure Description

[0022] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, 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 embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0023] Figure 1 The working principle of the REu-LDH nanomaterial of this invention is explained.

[0024] Figure 2 This is a TEM image of the REu-LDH nanomaterial obtained in Example 1.

[0025] Figure 3 The particle size variation of the REu-LDH nanomaterials obtained in Example 1 in different environments over 7 days (n=3).

[0026] Figure 4 The Fourier transform infrared spectra of RES, Eu-LDH, and REu-LDH in Example 1 are shown.

[0027] Figure 5 In the figure, A and B represent the DPPH scavenging activity of REu-LDH and the UV-Vis absorption spectra of DPPH at different europium doping levels, respectively.

[0028] Figure 5 In the middle (C), there are ROS fluorescence images of MLE-12 cells after treatment in each group.

[0029] Figure 6 In the figures A and B, the lung IVIS images and quantitative analysis of mice in the control group and IR group after injection of REu-LDH are shown at different time points, respectively.

[0030] Figure 7 In the figure, A, B, and C represent the TNF-α, IL-1β, and MDA levels of each group in the preliminary experiment, respectively.

[0031] Figure 8 This is a schematic diagram of an in vivo experiment.

[0032] Figure 9 This is a curve showing the change in mouse body weight during in vivo experiments.

[0033] Figure 10 In the figures, A, B, and C represent the MDA content, SOD enzyme activity, and GSH content in mouse lung tissue on days 7, 14, and 28 after in vivo irradiation, respectively (n=3).

[0034] Figure 11In the figures, A, B, and C represent the TNF-α, IL-6, and IL-1β levels in mouse lung tissue on days 7, 14, and 28 of in vivo irradiation, respectively (n=3).

[0035] Figure 12 In the figures, A, B, and C represent the IFN-γ, IL-13, and IL-4 levels in mouse lung tissue on days 7, 14, and 28 of in vivo irradiation, respectively (n=3).

[0036] Figure 13 In the image, A and B are representative images of HO-1 fluorescence staining after treatment in each group of the in vivo experiment (scale bar: 200 μm) and quantitative fluorescence intensity (n=3).

[0037] Figure 14 Representative images of H&E staining of major tissues and organs in mice of the control group and REu-LDH group in vivo (scale bar: 100 μm). Detailed Implementation

[0038] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0039] Example 1 A method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials includes the following steps: (1) First, 3.6 mmol Co(NO3)2·6H2O and a total of 1.2 mmol Al(NO3)3·9H2O and EuCl3·6H2O were dissolved in deionized water to obtain solution A (Al 3+ Eu 3+ The molar ratio of NaOH to Na2CO3 is 1:0.2. Dissolve 9.6 mmol NaOH and 2.4 mmol Na2CO3 in deionized water to obtain solution B. (2) Under nitrogen protection and magnetic stirring, solution A and solution B were simultaneously added dropwise to a reaction system containing 20 mL of deionized water, and the pH of the system was maintained at 10.0±0.02. After the addition was completed, the reaction mixture was transferred to a polytetrafluoroethylene-lined reactor and hydrothermally reacted at 130 °C for 10 h. After the reaction was completed, the precipitate was washed until neutral and lyophilized to obtain Eu-LDH powder. (3) Resveratrol (RES) was dissolved in ethanol and Eu-LDH dispersion was added. The mass ratio of resveratrol to Eu-LDH powder was 1:1. The mixture was magnetically stirred for 24 hours under light-protected conditions to load resveratrol into the LDH interlayer structure. After the reaction was completed, the unbound resveratrol was removed by centrifugation, and the mixture was washed 3 times and then freeze-dried to obtain the REu-LDH nanomaterial.

[0040] Figure 1 The working principle of the REu-LDH nanomaterial of this invention is explained.

[0041] Figure 2 The image shows a TEM image of the REu-LDH nanomaterial obtained in Example 1. REu-LDH exhibits a typical layered nanosheet structure with a regular overall morphology, relatively uniform layer distribution, clear boundaries, and no obvious aggregation observed. The nanosheets are relatively uniform in size, and the layered structure is intact.

[0042] Figure 3 The particle size change (n=3) of the REu-LDH nanomaterials obtained in Example 1 under different environments over 7 days is shown. To evaluate the dispersion stability of the REu-LDH nanosystem, it was dispersed in physiological saline, DMEM medium, and PBS buffer, respectively, and incubated at room temperature for 7 days, with periodic monitoring of hydrated particle size changes. The particle size of REu-LDH did not show significant changes throughout the monitoring period in different media, remaining within a relatively stable range. This indicates that the nanomaterial exhibits good dispersion stability in various physiologically relevant environments. These results demonstrate that REu-LDH possesses good stability, providing a solid foundation for its subsequent in vitro cell experiments and in vivo biological applications.

[0043] Figure 4 The images show the Fourier transform infrared spectra of RES, Eu-LDH, and REu-LDH from Example 1. Compared to Eu-LDH, the REu-LDH spectrum retains the hydroxyl vibration peak of LDH and also shows the characteristic absorption peak of RES. For example, at approximately 1600 cm⁻¹... -1 Aromatic ring C=C stretching vibration peaks can be observed nearby, at 1200-900 cm⁻¹. -1 The region exhibits CO and CH vibrational peaks associated with the polyphenol structure. Furthermore, REu-LDH shows peaks at approximately 1510 cm⁻¹. -1 (Aromatic ring C=C stretching vibration) and approximately 1270 cm -1 The absorption peak at the (phenolic hydroxyl CO stretching vibration) showed a certain degree of red shift compared to RES, suggesting that hydrogen bonding may have formed between RES and LDH. Meanwhile, at approximately 3440 cm⁻¹... -1A strong and broad OH stretching vibration absorption peak was observed, indicating the presence of abundant hydroxyl structures in the material, which is beneficial for improving the dispersibility of REu-LDH in aqueous solution. These results demonstrate that RES has been successfully bound and loaded into the layered structure of LDH.

[0044] Based on Example 1, the feed ratio of Al and Eu elements was changed: n(Al) 3+ ) = (1.2-x)mmol, from which REu can be obtained x LDH. Samples with different europium doping levels were prepared, including: LDH group (without Eu), Eu group... 0.1 -LDH group, Eu 0.2 -LDH group, Eu 0.4 -LDH group and Eu 0.6 -LDH group. Then load RES to obtain R-LDH, REu 0.1 -LDH, REu 0.2 -LDH, REu 0.4 -LDH and REu 0.6 -LDH, their antioxidant capacity was compared and evaluated by detecting the scavenging of DPPH.

[0045] Next, the antioxidant capacity of samples with different europium doping levels was verified at the cellular level. MLE-12 cells were seeded in 6-well plates (2 × 10⁻⁶ cells / well). 5 / hole), divided into Control group, IR group, R-LDH group, REu 0.1 -LDH group, REu 0.2 -LDH group, REu 0.4 -LDH group and REu 0.6 -LDH group. When MLE-12 cells adhered and grew to approximately 60% confluence, a single dose was administered at room temperature. 60 Cells were irradiated with 10 Gy of Co-γ rays, while the control group received no treatment. Immediately after irradiation, samples with different europium doping levels were added and cultured for 24 h. The culture medium was discarded, and 5 μM DCFH-DA working solution was prepared and added to each well. The cells were incubated at 37°C in the dark for 20 min. Cells were then washed three times with 1×PBS to remove any DCFH-DA that had not entered the cells. 1×Hoechst live cell staining solution was added, and the cells were incubated at 37°C for 10 min. After washing with PBS, intracellular ROS levels were observed and recorded under a fluorescence microscope.

[0046] DPPH free radical scavenging experiment: Prepare a 100 µg / mL DPPH ethanol solution and store it in the dark for later use. Mix the sample solutions with different concentrations and the DPPH solution in a certain volume ratio, shake well, and react in the dark at room temperature for 30 min. Use absolute ethanol instead of the sample as a blank control. After the reaction, measure the absorbance values (A) of each group of samples at a wavelength of 517 nm using an enzyme-labeling instrument. Calculate the DPPH free radical scavenging rate based on the absorbance changes between the control group and the experimental group:

[0047] where A control is the absorbance of the control group and A sample is the absorbance of the sample treatment group.

[0048] Figure 5 In A and B, the DPPH scavenging activity of REu-LDH and the UV-visible absorption spectrum of DPPH under different europium doping levels are respectively shown. Figure 5 In C, the ROS fluorescence images of MLE-12 cells after each group of treatments are shown. The results consistently show that REu 0.2 -LDH exhibits the best antioxidant performance, further confirming that this doping ratio (i.e., the molar ratio of REu 0.2 -LDH, Co 2+ :(Al 3+ +Eu 3+ ) is 3:1) represents the best balance between structural stability and catalytic efficiency.

[0049] Animal experiments Experimental animals: SPF-grade male C57BL / 6J mice, 6 - 8 weeks old, weighing 20 - 22 g, purchased from SpfBioscience Co., Ltd., animal production license number: SCXK(Beijing)2024 - 0001. The mice were housed under standard conditions: temperature 24 - 26 °C, humidity 55% - 65%, 12 h light / dark cycle, with free access to food and water.

[0050] I. Preliminary experiment Prior to formal in vivo experiments, preliminary experiments were conducted to determine the optimal dosing regimen. Mice were randomly assigned to the following groups: control group, IR group, IR + 2.5 mg / kg REu-LDH group, IR + 5 mg / kg REu-LDH group, and IR + 10 mg / kg REu LDH group. Except for the control group, mice in the other groups were anesthetized by intraperitoneal injection of 1% sodium pentobarbital. After the righting reflex disappeared and breathing stabilized, the mice were fixed in a custom-designed irradiation device. The chest area was marked as the irradiation center, and the head, neck, abdomen, and limbs were shielded with lead bricks, exposing only the chest. Subsequently, a single 20 Gy 60Co γ-ray irradiation was administered to the chest area to establish the RILI model. After irradiation, the mice were removed from the device and placed in a warm environment to awaken. Mice in each treatment group were immediately injected with the corresponding reagent via the tail vein. After euthanizing the mice, the lung tissue was quickly removed and gently rinsed with pre-cooled PBS buffer. 100 mg of lung tissue was weighed and placed in a pre-chilled homogenization tube. Nine volumes of tissue lysis buffer (1:9 w / v ratio) were added, and the tube was homogenized thoroughly using a tissue homogenizer under ice bath conditions. After homogenization, the tube was centrifuged at 12,000 rpm for 10 min at 4°C, and the supernatant was collected. TNF-α and IL-1β levels were detected using an ELISA kit, and MDA levels were detected using an MDA kit to assess anti-inflammatory and antioxidant effects.

[0051] Figure 7 In the figures, A, B, and C represent the levels of TNF-α, IL-1β, and MDA in the preliminary experimental groups, respectively. Compared with the IR group, all treatment groups showed varying degrees of reduction in inflammatory cytokines and oxidative stress markers. Notably, the 5 mg / kg REu-LDH group showed the most significant reductions in TNF-α, IL-1β, and MDA, while the 10 mg / kg REu-LDH group did not provide any additional improvement, indicating that the efficacy tended to plateau. Therefore, 5 mg / kg REu-LDH was selected as the optimal in vivo treatment dose for subsequent in vivo experiments.

[0052] II. In vivo imaging of small animals to investigate the biodistribution of REu-LDH in vivo Indocyanine green (ICG) was used as a fluorescent probe to label REu-LDH nanoparticles. Control group mice received no irradiation, while IR group mice received a single 20 Gy dose to the chest region. 60 Mice were irradiated with Co gamma rays. Following irradiation, both groups of mice were injected with ICG-REu-LDH via the tail vein. Mice were sacrificed at 1, 3, 6, 12, and 24 hours post-administration, and their lungs were collected. The distribution of REu-LDH in various tissues was detected using an in vivo imaging system (IVIS).

[0053] Figure 6 Images A and B in the table show lung IVIS images and quantitative analyses at different time points after REu-LDH injection in the control and IR groups of small animal in vivo imaging mice, respectively. This demonstrates that REu-LDH can be well enriched in the lungs after irradiation.

[0054] III. In vivo experiments Eight-week-old male C57BL / 6 mice were used to establish an RILI model for treatment studies. All animals were acclimatized under standard laboratory conditions for one week to minimize the impact of environmental stress on the experimental results. Subsequently, the mice were randomly divided into five groups: Control group, IR group, IR + Eu-LDH group, IR + RES group, and IR + REu-LDH group. Except for the Control group, the other groups received a single dose of 20 Gy of [unspecified substance]. 60 Mice were irradiated with Co-γ rays. Immediately after irradiation, mice in each treatment group were injected via the tail vein with Eu-LDH, RES, REu-LDH, and PBS, respectively, and the administration was repeated every other day for the following week. On days 7, 14, and 28 post-irradiation, six mice from each group were sacrificed (cervical dislocation method). Lung tissue was removed using sterile surgical instruments.

[0055] Figure 8 This is a schematic diagram of an in vivo experiment.

[0056] Figure 9 The graph shows the body weight change of mice during the in vivo experiment. Mouse body weight was continuously monitored from day 1 before irradiation to day 28 after irradiation. Compared with the control group, the irradiated mice showed a significant decrease in body weight, indicating successful model establishment. After treatment, the body weight of all groups gradually recovered, with the REu-LDH group showing the most significant recovery.

[0057] (1) REu-LDH reduces the level of oxidative stress in the body Figure 10 Tables A, B, and C show the MDA content, SOD enzyme activity, and GSH content in the lung tissue of RILI mice on days 7, 14, and 28 after in vivo irradiation, respectively (n=3). The results showed that radiation treatment significantly increased MDA levels while significantly decreasing SOD activity and GSH content, indicating severe damage to the body's antioxidant defense capabilities. REu-LDH treatment significantly alleviated these changes, gradually restoring antioxidant capacity to near-normal levels.

[0058] (2) REu-LDH inhibits the inflammatory response in vivo. Figure 11In the figures A, B, and C, the levels of TNF-α, IL-6, and IL-1β in the lung tissue of RILI mice were observed on days 7, 14, and 28 after in vivo irradiation, respectively (n=3). Radiation treatment significantly increased the expression of these three pro-inflammatory factors, particularly in the mid-to-late stages of lung injury (days 14 and 28). Compared to Eu-LDH and RES, REu-LDH significantly reduced the levels of pro-inflammatory factors, demonstrating a more prominent role in inflammation regulation.

[0059] (3) Figure 12 In the figures A, B, and C, the levels of IFN-γ, IL-13, and IL-4 in the lung tissue of RILI mice were observed on days 7, 14, and 28 after in vivo irradiation, respectively (n=3). Imbalance in the Th1 / Th2 immune response is considered one of the important mechanisms of RILI progression. Ionizing radiation can cause extensive epithelial and endothelial damage, releasing damage-associated molecular patterns, thereby activating the innate immune response and promoting naïve CD4+. + T cells differentiate into the Th1 phenotype, characterized by increased IFN-γ secretion and the initiation of an excessive inflammatory response. As injury progresses, the immune response gradually shifts towards Th2 cytokines (such as IL-4 and IL-13), thereby inducing fibroblast activation, collagen deposition, and subsequent fibrotic remodeling. REu-LDH treatment significantly modulates the Th1 / Th2 immune balance, inhibiting Th1-mediated inflammatory responses in the early stages while limiting excessive Th2 activation in the later stages, thus effectively blocking the transformation of inflammation into fibrosis.

[0060] (4) REu-LDH increases the expression level of HO-1 in vivo. Figure 13 In the figures, A and B represent representative images (scale bar: 200 μm) of HO-1 fluorescence staining after treatment in each group of the in vivo experiment, and quantitative fluorescence intensity (n=3), respectively. Heme oxygenase-1 (HO-1), as an important downstream effector molecule of the Nrf2 signaling pathway, plays a crucial role in protecting lung tissue from oxidative stress and inflammatory damage. REu-LDH treatment significantly upregulated HO-1 expression levels, indicating that its protective effect not only comes from direct ROS scavenging but may also exert its effect through activation of the Nrf2-HO-1 pathway. The increase in HO-1 expression levels is consistent with the decrease in inflammatory response, which is also consistent with the decrease in the expression of inflammatory factors.

[0061] (5) Figure 14Representative H&E staining images of major tissues and organs from mice in the in vivo experimental control group and REu-LDH group (scale bar: 100 μm). H&E staining of major organs in mice was performed to further evaluate the in vivo biocompatibility of REu-LDH. Compared with the control group, no obvious structural abnormalities were observed in the heart, liver, spleen, lungs, and kidneys of mice treated with REu-LDH. The structures of all organs and tissues were intact, with regular cell arrangement, and no obvious pathological changes such as inflammatory cell infiltration, cell necrosis, or tissue destruction were observed. This further demonstrates that REu-LDH has good tissue biocompatibility.

[0062] As can be seen, through the synergistic effects of the above-mentioned multiple mechanisms, the REu-LDH nanosystem constructed in this invention can simultaneously exert antioxidant, anti-inflammatory, and immunomodulatory effects, thereby effectively alleviating radiation-induced lung injury and promoting the recovery of lung tissue function. REu-LDH can improve the enrichment of drugs at the lesion site, exhibits good stability in various systems, and also has good biosafety, making it suitable for biomedical applications.

[0063] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials, characterized in that, Includes the following steps: (1) First, dissolve Co(NO3)2·6H2O, Al(NO3)3·9H2O and EuCl3·6H2O in deionized water to obtain solution A; dissolve NaOH and Na2CO3 in deionized water to obtain solution B; (2) Under nitrogen protection and magnetic stirring conditions, solution A and solution B were simultaneously added dropwise to the reaction system, and the pH of the system was maintained. After the addition was completed, the reaction mixture was transferred to the reaction vessel for hydrothermal reaction. After the reaction was completed, the precipitate was washed to neutral and freeze-dried to obtain Eu-LDH powder. Water was added to obtain Eu-LDH dispersion. (3) Dissolve resveratrol in ethanol, add Eu-LDH dispersion, and stir magnetically under light-protected conditions to load resveratrol into the LDH interlayer structure; after the reaction is completed, centrifuge to remove unbound resveratrol, wash 2-3 times and freeze dry to obtain the final product.

2. The method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials according to claim 1, characterized in that, In step (1), Co 2+ : (Al 3+ + Eu 3+ ) is 3:1; Al 3+ : Eu 3+ is 1:0.

2.

3. The method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials according to claim 1, characterized in that, In step (1), the molar ratio of NaOH to Na2CO3 is 4:

1.

4. The method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials according to claim 1, characterized in that, In step (2), the pH of the maintenance system is 10.0 ± 0.

02.

5. The method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials according to claim 1, characterized in that, In step (2), the hydrothermal reaction is carried out at a temperature of 130°C for 10 hours.

6. The method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials according to claim 1, characterized in that, In step (3), the mass ratio of resveratrol to Eu-LDH powder is 1:

1.

7. The method for preparing resveratrol-supported europium-doped layered double hydroxide nanomaterials according to claim 1, characterized in that, In step (3), the magnetic stirring time is 24 h.

8. Nanomaterials obtained by the preparation method according to any one of claims 1-7.

9. The application of the nanomaterial according to claim 8 in the preparation of drugs to alleviate radiation-induced lung injury.

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