A drug-loaded nanomotor targeting acute lung injury, its preparation and application

Abstract

This invention provides a method for preparing a drug-loaded nanomotor targeting acute lung injury. Studies have shown that this drug-loaded nanomotor exhibits better anti-inflammatory effects compared to tetracycline alone. In particular, it significantly improves inflammatory lung injury and significantly reduces systemic / local inflammatory responses. This also confirms that the motor can enhance drug efficacy and is expected to reduce drug side effects.

Description

Technical Field

[0001] This invention relates to the field of chemical methods, specifically to the field of chemical synthesis of nanocarriers, and more specifically to a drug-loadable nanomotor for targeting acute lung injury, a tetracycline-loaded nanomotor, the preparation of the nanomotor and its application in targeting acute lung injury. Background Technology

[0002] Acute lung injury is one of the major causes of death and disability in critically ill patients. Currently, there is a lack of effective treatments. Excessive activation of inflammatory cells and oxidative stress damage are the core pathophysiological mechanisms of acute lung injury.

[0003] Tetracycline (TH) is a broad-spectrum antibiotic produced by actinomycetes. Recent studies have found that it can alleviate inflammatory damage by inhibiting Caspase-1 and selectively inhibiting the release of IL-1β and IL-18, representing a novel approach for treating acute lung injury. However, systemic, high-dose, and long-term use of tetracycline has serious side effects, including hepatotoxicity, nephrotoxicity, photosensitivity, dental and bone toxicity, increased intracranial pressure, and dysbiosis, limiting its application, especially in critically ill patients. For patients with acute lung injury, local administration of tetracycline would significantly reduce side effects and potentially improve therapeutic efficacy through targeted drug delivery. However, tetracycline currently lacks indications for intratracheal administration. Therefore, optimizing the administration method of tetracycline and improving its targeting are crucial research methods to further enhance its efficacy. Summary of the Invention

[0004] The present invention aims to overcome the above-mentioned defects and provide a composite nanomotor that can facilitate precise drug delivery, increase tissue permeability, and improve therapeutic efficacy.

[0005] This invention provides a method for preparing drug-loaded nanomotors targeting acute lung injury, which involves reacting diisopropylamine-diazepine (PAPA / NO) with methacrylic anhydride or methacrylic acid or methacrylate to generate methacryloyl PAPA / NO, and then reacting it with N,N'-bisacryloylcysteine ​​to obtain the nanomotor MPN.

[0006] The synthesis method of methacrylamide PAPA / NO is as follows: diisopropylamine-diazepinel salt, water and 1,4-dioxane are mixed, and triethylamine is added dropwise. Then, methacrylic anhydride or methacrylic acid or methacrylate salt is added dropwise while stirring under ice-water bath cooling conditions. After the dropwise addition is completed, the reaction is stirred at room temperature overnight. After the reaction is completed, acetone is added to the reaction solution to precipitate and obtain methacrylamide PAPA / NO.

[0007] The molar ratio of diisopropylamine-diazepine to methacrylic anhydride, methacrylic acid, or methacrylate is 1:(1-2); the amount of diisopropylamine-diazepine, water, and 1,4-dioxane added is 1 ml-5 ml of water and 0.5 ml-2 ml of 1,4-dioxane per mmol of diisopropylamine-diazepine; the molar amount of triethylamine added is 2-3 times the molar amount of diisopropylamine-diazepine.

[0008] The process of obtaining the nanomotor MPN by further reacting methacrylated PAPA / NO with N,N'-bisacryloylcysteamine is as follows: N,N'-bisacryloylcysteamine and methacrylated PAPA / NO are dissolved in buffer solution and ultrasonically mixed. After deoxygenation by purging with nitrogen for 30 minutes, an initiator and catalyst are added under continuous nitrogen protection. The reaction is stirred at room temperature until the solution becomes turbid. After centrifugation, washing with water, and freeze-drying, the nanomotor MPN is obtained.

[0009] The molar ratio of methacrylated PAPA / NO to N,N'-bisacryloylcysteine ​​is (1-10):1; the initiator is selected from ammonium persulfate; the catalyst is selected from N,N,N',N'-tetramethylethylenediamine; the amount of initiator added is 1%-10% of the total weight of the system; the amount of catalyst added is 5%-15% of the total weight of the system.

[0010] Furthermore, the method for preparing a drug-loaded nanomotor targeting acute lung injury provided by the present invention also has the following characteristics: the reaction process of methacrylylated PAPA / NO with N,N'-bisacryloylcysteine ​​is carried out in a phosphate buffer system.

[0011] Furthermore, the present invention also provides a tetracycline-loaded nanomotor, characterized in that tetracycline is loaded onto the nanomotor MPN prepared according to the above method.

[0012] The preparation method is as follows: MPN nanomotors are dispersed in a buffer solution containing tetracycline, stirred at room temperature for 10-24 hours, and then collected by centrifugation to obtain MPN@TH nanomotors;

[0013] The mass ratio of the nanomotor MPN to tetracycline is 1:(0.5-1).

[0014] In addition, this invention also suggests the application of tetracycline-loaded nanomotors in the preparation of anti-inflammatory drugs.

[0015] In addition, this invention also suggests the application of tetracycline-loaded nanomotors in the preparation of drugs for treating, alleviating and preventing inflammatory lung injury, and reducing systemic / local inflammatory responses.

[0016] In addition, this invention also suggests the application of tetracycline-loaded nanomotors in the preparation of formulations that inhibit inflammatory factors and suppress the INF-β signaling pathway.

[0017] The function and effects of this invention:

[0018] This invention involves reacting diisopropylamine-diazepine PAPA / NO with methacrylic anhydride, methacrylic acid, or methacrylate to generate methacrylylated PAPA / NO, followed by further reaction with N,N'-bisacryloylcysteine ​​to obtain a novel drug-loaded nanomotor, MPN (synthetic route as follows). Figure 6 (As shown). Diisopropylamine-diazepinel salt PAPA / NO was first used in the development of drug-loaded nanomotors. In this study, it was found that this drug-loaded nanomotor can be used to load anti-inflammatory drugs, such as tetracycline. Furthermore, this study found that when tetracycline is loaded onto this drug-loaded nanomotor MPN, it achieves a better anti-inflammatory effect than tetracycline alone. Specifically, the tetracycline-loaded nanomotor MPN exhibits more significant anti-inflammatory effects than tetracycline in improving inflammatory lung injury and reducing systemic / local inflammatory responses. Therefore, this study demonstrates that this nanomotor has the function of improving drug efficacy. Attached Figure Description

[0019] Figure 1 Characterization of MPN nanomotors and MPN@TH nanomotors

[0020] (a) Zeta potential; (b) Dynamic light scattering (DLS) particle size distribution results; (c) Cumulative TH release curve of MPN@TH in PBS over 24 hours; (d) Cumulative TH release curve of PB@TH in PBS over 24 hours; (e) Comparison of drug loading of MPN@TH and PB@TH.

[0021] Figure 2 The therapeutic effect of .MPN@TH on inflammatory lung injury in ALI mice

[0022] (a) Typical H&E staining images of lung tissue from ALI mice. (b) Differences in lung injury scores among groups, including total injury score, alveolar neutrophil infiltration score, interstitial centrogranulocyte infiltration score, hyaline membrane score, protein debris score, and alveolar membrane thickening score. TH, PB@TH, and MPN@TH interventions all significantly improved LPS-mediated lung injury, with MPN@TH showing significantly better therapeutic effects than TH monotherapy and non-motor-loaded PB@TH (statistical analysis was performed using the Kruskal-Wallis test and Dunn's multiple comparison method; data are expressed as mean ± standard deviation. * indicates P < 0.05, ** indicates P < 0.01, *** indicates P < 0.001).

[0023] Figure 3 .MPN@TH reduces systemic inflammatory response in ALI mice

[0024] (a) Blood routine test results of ALI mice; (b) Heatmap analysis of multiple inflammatory factors in the serum of ALI mice; (c) Quantitative results of representative cytokines detected by ELISA (statistical analysis was performed using Kruskal-Wallis test and Dunn multiple comparison method, and the data are expressed as mean ± standard deviation. * indicates P<0.05, ** indicates P<0.01, *** indicates P<0.001).

[0025] Figure 4 .MPN@TH reduces local inflammatory response in ALI mice

[0026] (a) Changes in the number of neutrophils in bronchoalveolar lavage fluid (BALF); (b) Changes in the number of macrophages in BLF; (c) Changes in the mean fluorescence intensity (MFI) of CD86 macrophages in BLF; (d) Changes in the mean fluorescence intensity (MFI) of CD206 macrophages in BLF; (e) Immunofluorescence showed changes in the expression levels of IL-1β (green fluorescence), IL-6 (red fluorescence), and TNFα (pink fluorescence) in lung tissue. Statistical analysis was performed using the Kruskal-Wallis test and Dunn's multiple comparison method. Data are expressed as mean ± standard deviation. * indicates P < 0.05, ** indicates P < 0.01, and *** indicates P < 0.001.

[0027] Figure 5 Transcriptome sequencing revealed that MPN@TH exerts a therapeutic effect on ALI mice through mechanisms such as inhibition of inflammatory responses, neutrophil chemotaxis, and activation of cytokines like interferon.

[0028] Figure 6 Synthetic route using methacrylic anhydride as an example, where PAPA / NO: diisopropylamine-diazepinel salt, TEA: triethylamine, MAC: methacrylic anhydride, AS: ammonium sulfate, TMEDA: N,N,N',N'-tetramethylethylenediamine, MPN: nanomotor, MPN@TH: tetracycline-loaded nanomotor. Detailed Implementation

[0029] This invention is capable of various modifications and embodiments, and therefore specific embodiments are illustrated and described in the accompanying drawings. However, this is not intended to limit the invention to specific implementations, but should be understood to include all modifications, equivalents, and even substitutions that fall within the spirit and scope of this invention.

[0030] Example 1. Synthesis method of MPN nanomotors:

[0031] The diisopropylamine-diazepine salt is reacted with methacrylic anhydride or methacrylic acid or methacrylate to generate methacryloyl PAPA / NO, which is then further reacted with N,N'-bisacryloylcysteine ​​to obtain the nanomotor MPN.

[0032] The synthesis method of methacrylamide PAPA / NO is as follows: diisopropylamine-diazepinel salt, water and 1,4-dioxane are mixed, and triethylamine TEA is added dropwise to the mixture. Then, methacrylic anhydride or methacrylic acid or methacrylate salt is added dropwise while stirring under ice-water bath cooling. After the addition is completed, the mixture is stirred at room temperature overnight. After the reaction is completed, acetone is added to the reaction solution as a precipitating agent to precipitate and obtain methacrylamide PAPA / NO.

[0033] The molar ratio of diisopropylamine-diazepine to methacrylic anhydride (MAC), methacrylic acid (MMA), or methacrylate is 1:1-2; the amount of diisopropylamine-diazepine, water, and 1,4-dioxane added is 1-5 ml of water and 0.5-2 ml of 1,4-dioxane per mmol of diisopropylamine-diazepine; the molar amount of triethylamine added is 2-3 times the molar amount of diisopropylamine-diazepine.

[0034] The process of obtaining nanomotors MPN by further reacting methacrylated PAPA / NO with N,N'-bisacryloylcysteamine is as follows: N,N'-bisacryloylcysteamine and methacrylated PAPA / NO are dissolved in a buffer solution (any commonly used buffer solution is acceptable), ultrasonically mixed, and then deoxygenated by nitrogen for 30 minutes. Subsequently, an initiator and a catalyst are added under continuous nitrogen protection, and the reaction is stirred at room temperature until the solution becomes turbid. After post-treatment, nanomotors MPN are obtained. Among them, the initiator is selected from ammonium persulfate (AS), and the catalyst is selected from N,N,N',N'-tetramethylethylenediamine (TMEDA).

[0035] The molar ratio of methacrylated PAPA / NO to N,N'-bisacryloylcysteine ​​is 1-10:1; the amount of initiator added is 1-10% of the total weight of the system; and the amount of catalyst added is 5-15% of the total weight of the system.

[0036] The optimal test example is as follows:

[0037] 1. Synthesis of tetracycline-loaded nanomotors (MPN@TH)

[0038] 1.1. Synthesis of diisopropylamine-diazepinel salt derivatives

[0039] First, diisopropylamine-diazepine (PAPA / NO) (1.94 g, 12 mmol, Maclean's reagent, HY-134636) was dissolved in a mixture of distilled water (20.0 mL) and 1,4-dioxane (8.5 mL, Sinopharm Chemical Reagent Co., Ltd.). Then, triethylamine (4.5 mL, 32.3 mmol, Aladdin Chemical Co., Ltd.) was added dropwise to the mixture. After cooling the reaction system in an ice-water bath, methacrylic anhydride (3.0 mL, 18.9 mmol, Aladdin Chemical Co., Ltd.) was slowly added dropwise with stirring over a period of 10 minutes. The ice-water bath was removed, and the reaction was stirred overnight at room temperature. The product was obtained by two reprecipitations using 400.0 mL of acetone, followed by vacuum drying at 60 °C. This final product was named methacrylamide PAPA / NO, abbreviated as MPN.

[0040] 1.2. Synthesis of MPN Nanomotors

[0041] First, N,N'-bisacryloylcysteine ​​(BAC, 2.00 mg, 0.0077 mmol, Shanghai Maclean Biotechnology Co., Ltd.) and MPN (9.25 mg, 0.0285 mmol) were dissolved in phosphate-buffered saline (PBS, 2.0 mL) and sonicated. The solution was deoxygenated by purging with nitrogen for 30 minutes. Then, under continuous nitrogen protection, the initiator ammonium persulfate (APS, 4% of the total system, 0.45 mg, Shanghai Maclean Biotechnology Co., Ltd.) and N,N,N',N'-tetramethylethylenediamine (TEMED, 8% of the total system, 0.90 mg, Shanghai Aladdin Biotechnology Co., Ltd.) were added. The reaction was stirred at room temperature for 2 hours until the solution became turbid. The product was centrifuged (8000 rpm, 10 minutes), washed twice with water, and then lyophilized to obtain a white solid.

[0042] 1.3. Synthesis of non-nanomotor PB

[0043] BAC (12.00 mg, 0.0462 mmol) was dissolved in PBS (2.0 mL) and sonicated. The solution was deoxygenated by purging with nitrogen for 30 minutes. Under continuous nitrogen protection, initiator APS (4% of the total system, 0.48 mg) and TEMED (8% of the total system, 0.96 mg) were added. The reaction was stirred at room temperature for 2 hours until turbidity appeared. The product was centrifuged (8000 rpm, 10 min), washed twice with water, and then lyophilized to obtain a white solid, designated as PB non-nanomotor. PB (20 mg) was dispersed in PBS solution containing TH (5 mL, 2.5 mg / mL) and stirred at room temperature for 12 hours. After centrifugation, the white solid was collected and named PB@TH non-nanomotor.

[0044] Example 2. Preparation method of tetracycline-loaded nanomotor:

[0045] The MPN nanomotor was dispersed in a buffer solution containing tetracycline and stirred at room temperature for 10-24 hours. The MPN@TH nanomotor was then collected by centrifugation. The mass ratio of MPN to tetracycline was 1:0.5-1.

[0046] The optimal test example is as follows:

[0047] 1.4. Fabrication of MPN@TH nanomotors

[0048] MPN (20 mg) was dispersed in 5 mL of PBS solution containing TH (2.5 mg / mL) and stirred at room temperature for 12 hours. After centrifugation, the white solid was collected and named MPN@TH nanomotor.

[0049] Example 3. Results and Characterization

[0050] 1. Characterization of nanomotors

[0051] The size of nanoparticles (NPs) was analyzed using an HT7800 transmission electron microscope (Hitachi, Japan). Zeta potentials and particle size distributions were determined using a Nano-Z Zetasizer nanoparticle size and zeta potential analyzer (Malvin Instruments, UK). The ¹H NMR spectra of the samples were acquired using a Bruker Avance 400 NMR spectrometer. Absorbance at 360 nm was measured using an automated microplate reader (Tecan (Shanghai) Experimental Equipment Co., Ltd., Switzerland). Fourier transform infrared (FT-IR) spectroscopy was obtained using a Cary 5000 FT-IR spectrometer (Varian, USA). The movement trajectories of the nanomotors in the cellular environment were recorded using a fluorescence microscope (MF53-N, Guangzhou Mingmei Optoelectronic Technology Co., Ltd.). Chemical structural formulas were drawn using ChemDraw Ultra 7.0 software.

[0052] RAW 264.7 macrophages (5 × 10⁻⁶) 4 Macrophages were seeded overnight in culture dishes. After stimulation with lipopolysaccharide (LPS, Shanghai Yisheng Biotechnology Co., Ltd.) for 12 hours, Cy5-labeled MPN@TH and PB@TH (200 μg / mL) were added. Unstimulated macrophages were added simultaneously to the control group samples. Motion trajectories were tracked using an inverted fluorescence microscope (×100 objective lens), and image sequences were analyzed using ImageJ software (v2.0.0). The average particle velocity was calculated by averaging the velocities over time intervals. Ten nanoparticles were tracked in each group to determine the average velocity and mean square displacement (MSD) values. Particle motion types were classified by MSD fitting. Results are shown below. Figure 1 .

[0053] 2. Validation of nanomotors in a mouse model: alleviating acute lung injury in mice.

[0054] Male C57BL / 6J mice aged 8-12 weeks (purchased from Cyagen Biosciences) were used. A brief description of the acute lung injury (ALI) model: After intraperitoneal injection of 80 mg / kg sodium pentobarbital for anesthesia, lung injury was induced by intratracheal instillation of 70 μL of PBS solution containing 160 μg LPS. Subsequently, 80 μL of PBS solution containing TH (1 μg / g), PB@TH (4.7 μg / g, of which TH is 1 μg / g), or MPN@TH (5.1 μg / g, of which TH is 1 μg / g) was instilled to evaluate the therapeutic efficacy of ALI. The sham-operated group was instilled with an equal volume of PBS as a control. Mice were sacrificed 24 hours after intervention, and peripheral blood, lung tissue, and bronchoalveolar lavage fluid (BALF) were collected for subsequent analysis.

[0055] To assess lung injury scores and local inflammatory responses, fixed sections of the left upper lobe of the lungs were taken from 3-4 mice in each group. HE staining was used to score five pathological features (alveolar neutrophil infiltration, interstitial neutrophil infiltration, hyaline membrane formation, alveolar protein exudate, and alveolar septal thickening). The severity of injury was assigned as 0, 1, or 2 points, and a weighted average was used to obtain a final score of 0-1. Results are shown below. Figure 2 This indicates the therapeutic effect of MPN@TH on inflammatory lung injury in ALI mice.

[0056] 3. Nanomotors alleviate systemic inflammatory response in mice with acute lung injury.

[0057] Blood routine tests: 24 hours after model establishment, anticoagulated blood samples were collected via cardiac puncture and analyzed by Wuhan ServiceBio Technology Co., Ltd. (website: https: / / www.servicebio.cn / ). Four mice were included in each experimental group.

[0058] Serum multiplex ELISA assay: Twenty-four days after modeling, 500 μL of whole blood was collected from each mouse, and serum was obtained by centrifugation (5000 rpm, 10 min). The resulting protein samples were used for multiplex ELISA assay (Boster Biological, catalog number MEK1003, factor 13 assay) to assess systemic inflammation levels. Each experiment included 3 mice. Results are shown below. Figure 3 This indicates that MPN@TH reduces systemic inflammatory response in ALI mice.

[0059] 4. Nanomotors alleviate local lung inflammation in mice with acute lung injury.

[0060] Immunofluorescence staining of lung tissue: Local inflammation analysis was performed by immunofluorescence staining to detect the expression of pro-inflammatory cytokines and activation of inflammatory cells. The primary antibodies used included: IL-1β (Abcam, TA5103, 1:200), IL-6 (Abcam, TD6087, 1:200), TNFα (Abcam, PY19810S, 1:500), F4 / 80 (Abcam, ab300421, 1:100), LY6G (Proteintech, 65078-1-Ig, 1:100) and CCR7 (Proteintech, 25898-1-AP, 1:200).

[0061] Bronchoalveolar lavage fluid flow cytometry analysis: After collecting bronchoalveolar lavage fluid from mice, immune cells were obtained by centrifugation at 350 g for 5 minutes, washed with PBS, and resuspended in 50 μL buffer. The following staining was performed sequentially: cell viability markers (Live / Dead) and immune cell activation markers. Data acquisition was performed using a BD FACSCanto II flow cytometer, and data analysis was performed using FlowJo software. After excluding diploids and dead cells, the following were identified: neutrophils: CD45+CD11b+Ly6G+ cell population; macrophages: CD45+CD11b+Ly6G- cell population. Macrophage polarization status was analyzed by assessing the mean fluorescence intensity (MFI) of CD86 and CD206. Each experiment included 3-4 mice.

[0062] Multiplex ELISA assay of lung tissue: Total protein was extracted from lung lobe tissue, and the concentration of total protein in lung tissue was determined using a BCA protein quantification kit. Subsequently, a multiplex ELISA assay kit (Boster Biological, catalog number MEK1003, factor 13 assay) was used to analyze the extracted proteins to assess the level of local inflammation. Three mice were used in each experimental group. Results are shown below. Figure 4 This indicates that MPN@TH reduces local inflammatory response in ALI mice.

[0063] 5. Transcriptome sequencing elucidates the therapeutic mechanism of nanomotors

[0064] Total RNA was extracted from the lower lobe of the left lung of mice using the Trizol method for sequencing analysis. Differential expression analysis was performed using the DESeq algorithm. A p-value <0.05 after error detection rate correction and log2FC >1 or <-1 were set as the screening threshold for differentially expressed genes (DEGs). Further gene ontology (GO) and gene set enrichment (GSEA) analyses were conducted on DEGs to explore their function and biological significance. Results are shown below. Figure 5 Transcriptome sequencing revealed that MPN@TH exerts a therapeutic effect on ALI mice through mechanisms such as inhibition of inflammatory responses, neutrophil chemotaxis, and activation of cytokines such as interferon.

[0065] The function and effect of this embodiment:

[0066] This study demonstrates that the drug-loaded nanomotor exhibits superior anti-inflammatory effects compared to tetracycline alone. Specifically, it significantly improves inflammatory lung injury and significantly reduces systemic and local inflammatory responses. This also confirms that the motor can enhance drug efficacy and may reduce drug side effects.

[0067] While the foregoing has focused on embodiments, these are merely illustrative and do not limit the invention. Those skilled in the art will understand that various modifications and applications not illustrated above can be made without departing from the essential characteristics of these embodiments. For example, the constituent elements specifically shown in the embodiments can be implemented through modifications. Furthermore, various differences related to such modifications and applications should be interpreted as being included within the scope of the invention as defined in the appended claims.

Claims

1. A method for preparing a drug-loaded nanomotor targeting acute lung injury, characterized in that: The diisopropylamine-diazepine salt is reacted with methacrylic anhydride or methacrylic acid or methacrylate to generate methacryloyl PAPA / NO, which is then further reacted with N,N'-bisacryloylcysteine ​​to obtain the nanomotor MPN. The method for synthesizing the methacrylamide PAPA / NO is as follows: diisopropylamine-diazepinel salt, water and 1,4-dioxane are mixed, and triethylamine is added dropwise. Then, methacrylic anhydride or methacrylic acid or methacrylate salt is added dropwise while stirring under ice-water bath cooling conditions. After the dropwise addition is completed, the reaction is stirred at room temperature overnight. After the reaction is completed, acetone is added to the reaction solution to precipitate and obtain methacrylamide PAPA / NO. The molar ratio of diisopropylamine-diazepine to methacrylic anhydride, methacrylic acid, or methacrylate is 1:(1-2); the amount of diisopropylamine-diazepine, water, and 1,4-dioxane added is 1 ml-5 ml of water and 0.5 ml-2 ml of 1,4-dioxane per mmol of diisopropylamine-diazepine; the molar amount of triethylamine added is 2-3 times the molar amount of diisopropylamine-diazepine. The process of further reacting methacrylated PAPA / NO with N,N'-bisacryloylcysteine ​​to obtain the nanomotor MPN is as follows: N,N'-bisacryloylcysteine ​​and methacrylated PAPA / NO are dissolved in a buffer solution and ultrasonically mixed. After deoxygenation by purging with nitrogen for 30 minutes, an initiator and catalyst are added under continuous nitrogen protection. The reaction is stirred at room temperature until the solution becomes turbid. After centrifugation, washing with water, and freeze-drying, the nanomotor MPN is obtained. The molar ratio of methacrylated PAPA / NO to N,N'-bisacryloylcysteine ​​is (1-10):1; the initiator is selected from ammonium persulfate; the catalyst is selected from N,N,N',N'-tetramethylethylenediamine; the amount of initiator added is 1%-10% of the total weight of the system; the amount of catalyst added is 5%-15% of the total weight of the system.

2. The method for preparing a drug-loaded nanomotor targeting acute lung injury as described in claim 1, characterized in that: The reaction of methacrylated PAPA / NO with N,N'-bisacryloylcysteine ​​was carried out in a phosphate buffer system.

3. A tetracycline-loaded nanomotor, characterized in that: Tetracycline is loaded onto the nanomotor MPN obtained by any of the preparation methods described in claims 1-2.

4. The method for preparing a tetracycline-loaded nanomotor as described in claim 3, characterized in that: The MPN nanomotor was dispersed in a buffer solution containing tetracycline, stirred at room temperature for 10-24 hours, and then collected by centrifugation to obtain the MPN@TH nanomotor. The mass ratio of the nanomotor MPN to tetracycline is 1:(0.5-1).

5. The application of the tetracycline-loaded nanomotor as described in claim 3 in the preparation of anti-inflammatory drugs.

6. The application of the tetracycline-loaded nanomotor as described in claim 3 in the preparation of medicaments for treating, alleviating and preventing inflammatory lung injury and reducing systemic / local inflammatory responses.

7. The application of the tetracycline-loaded nanomotor as described in claim 3 in the preparation of formulations that inhibit inflammatory factors and suppress the INF-β signaling pathway.

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