Platelet membrane-coated nanoparticles and their use in preparing drugs for treating sepsis-related acute lung injury

Abstract

The invention discloses a platelet membrane-coated nanoparticle and an application thereof in preparing a drug for treating sepsis-related acute lung injury. The platelet membrane is separated and extracted, and the platelet membrane is co-extruded with a nano-silica loading material to obtain the platelet membrane-coated nanoparticle, which has good biosafety, biocompatibility and high targeting ability, and can effectively treat ALI. The invention utilizes mesoporous silica to load two drugs, CeO2 nanozyme and sivelestat sodium, which work together to effectively inhibit NETs generation and enhance the ability to clear NETs, ​​thereby achieving the purpose of treating ALI. At the same time, the platelet membrane-coated nanoparticle can avoid clearance by the immune system, achieve targeted drug delivery, and has good biosafety and biocompatibility.

Description

Technical Field

[0001] The present invention relates to the field of biomedical technology, and in particular to a platelet membrane-coated nanoparticle and an application thereof in preparing a drug for treating sepsis-related acute lung injury. Background Art

[0002] The pathogenesis of sepsis is complex. The dysregulated inflammatory immune response caused by acute lung injury (ALI) is an important cause of the high mortality rate of sepsis. ALI manifests as non-cardiogenic pulmonary edema and hypoxemia. Therefore, it is necessary to develop precise and safe drug intervention measures for ALI.

[0003] Neutrophils are the first responders to infection and play a key role in host immune defense by rapidly recruiting to the site of infection, engulfing pathogens and producing microbicidal mediators. In 2004, Brinkmann et al. first proposed a new effector function of neutrophils, namely the formation of neutrophil extracellular traps (NETs). In recent years, the infiltration of neutrophils and the release of NETs have been shown to be involved in important pathological processes in the development of ALI. The formation of NETs further aggravates lung tissue damage and promotes inflammatory responses. Studies have shown that the removal of excessive NETs can inhibit the inflammatory response of LPS-induced ALI and reshape immune homeostasis. Therefore, effective removal of NETs in inflammatory lung tissue may be a potential strategy for the treatment of ALI.

[0004] The structural skeleton DNA of NETs and the main proteases attached to it, such as NE and myeloperoxidase (MPO), all play different roles in their formation. Recent studies have shown that reactive oxygen species (ROS) can promote the transfer of NE from particles to the nucleus, where NE processes histones, leading to the release of NETs into the extracellular space. Therefore, NE plays a key role in the formation of NETs, ​​and inhibiting the activity of NE may be a feasible method to prevent the formation of NETs. The degradation of DNA in NETs is the last step in targeting NETosis. DNAase can degrade the DNA backbone of NETs, ​​but DNase cannot inhibit the activity of proteases decorated on NETs. Therefore, the combined use of DNase and NE inhibitor SE can effectively inhibit the formation of excessive NETs. However, systemic inhibition of NETs is not conducive to preserving the intrinsic defense mechanism of the immune system and may lead to increased susceptibility to bacterial infections. In addition, these inhibitory drugs still face great problems in clinical use, such as poor targeting, short circulation half-life, poor pharmacokinetics and instability. New drug delivery strategies need to be designed to improve the uptake and utilization of drugs in the body.

[0005] At present, when researchers use NETs as a breakthrough point to treat ALI, they mainly focus on inhibiting or blocking a key substance in the main components of NETs. This treatment strategy has limitations such as insignificant efficacy and easy clearance by the body. The multiple inhibition of NETs has been fully applied in diseases such as tumors due to the multi-faceted clearance of NETs components. Although researchers have developed a variety of nanodrug delivery systems coated with cell membranes such as neutrophils and tumor cells to improve drug delivery efficiency, there is still a risk of being cleared by the body as foreign objects. The platelet membrane can inhibit the phagocytic effect of phagocytes due to the presence of specific proteins, thereby effectively avoiding clearance by the immune system and better exerting its pharmacological effects. However, there are no reports on the treatment of ALI with platelet membrane-coated drugs. Summary of the invention

[0006] In view of the deficiencies of the prior art, the object of the present invention is to provide a platelet membrane-coated nanoparticle and its use in the preparation of a drug for treating sepsis-related acute lung injury.

[0007] In order to achieve the above object, the present invention adopts the following technical scheme:

[0008] In a first aspect, the present invention provides a method for preparing platelet membrane-coated nanoparticles, comprising the following steps:

[0009] S1, dispersing mesoporous nano-silica and cerium oxide in deionized water, then adding sivelestat sodium solution thereto, stirring and mixing evenly, and centrifuging to obtain a nano-silica supported material;

[0010] S2, extracting and preparing platelet membrane from platelet-rich plasma;

[0011] S3, adding the platelet membrane obtained in step S2 and the nano-silica loaded material obtained in step S1 into deionized water, mixing them evenly and then ultrasonically treating them, and then repeatedly extruding them 10-30 times using a liposome extruder to obtain platelet membrane-coated nanoparticles.

[0012] In some embodiments of the present invention, in step S1, the preparation method of mesoporous nano-silica is as follows: cetyltrimethylammonium chloride (CTAC) and triethylamine (TEA) are added to deionized water, stirred evenly, and then mesitylene and ethyl orthosilicate are added, stirred for reaction, and after the reaction is completed, CTAC is removed by reflux of ethanol, centrifuged, and the resulting precipitate is mesoporous nano-silica (abbreviated as MSN).

[0013] Specifically, the usage ratio of hexadecyltrimethylammonium chloride, triethylamine, mesitylene and ethyl orthosilicate is 1.5-2.5 g: 0.01-0.03 g: 1-2 mL: 1-2 mL.

[0014] Specifically, the stirring reaction temperature is 80-95° C., and the stirring reaction time is 1-3 h.

[0015] In some embodiments of the present invention, in step S1, the preparation method of cerium oxide is as follows: cerium acetate and oleylamine are added to xylene, stirred at room temperature for 18-24 hours, then aged for 2-4 hours under nitrogen protection, and precipitated with acetone to obtain cerium oxide (CeO2).

[0016] Specifically, the mass ratio of cerium acetate to oleylamine is 0.4-0.5:3-4.

[0017] In some embodiments of the present invention, in step S1, the mass ratio of mesoporous nano-silica, cerium oxide and sivelestat sodium is 1:1-2:3-5. For example, 1:1:3, 1:1:4, 1:1:5, 1:1.5:3, 1:1.5:4, 1:1.5:5, 1:2:3, 1:2:4, 1:2:5 can be selected, but it is not limited to the listed values, and other unlisted values ​​within the numerical range are also applicable.

[0018] In some embodiments of the present invention, in step S2, the specific process for extracting and preparing platelet membrane is as follows: blood is collected from anesthetized mice, and platelet-rich plasma is obtained by centrifugation, which is added to a phosphate buffer containing EDTA to inhibit platelet activation, followed by centrifugation to collect platelet precipitates, and the platelet membrane precipitates are collected after repeated freezing and thawing at -80°C and centrifugation.

[0019] Specifically, the content of EDTA in the phosphate buffer is 0.5-2 mM.

[0020] In some embodiments of the present invention, in step S3, the mass ratio of the platelet membrane to the nano-silica loading material is 1-3:1.

[0021] In some embodiments of the present invention, in step S3, the ultrasonic power is 100-200 W, for example, 100 W, 120 W, 140 W, 150 W, 160 W, 180 W, and 200 W can be selected; the ultrasonic time is 5-10 min, for example, 5 min, 6 min, 7 min, 8 min, 9 min, and 10 min can be selected; but it is not limited to the listed values, and other values ​​not listed within the numerical range are also applicable.

[0022] In a second aspect, the present invention provides platelet membrane-coated nanoparticles prepared by the above preparation method.

[0023] In a third aspect, the present invention also provides the use of the platelet membrane-coated nanoparticles in the preparation of a drug for treating sepsis-related acute lung injury.

[0024] Specifically, the dosage form of the drug is injection, tablet, capsule, granule, pill, oral solution or emulsion.

[0025] Specifically, the drug also includes a pharmaceutically or pharmacologically acceptable carrier.

[0026] Compared with the prior art, the present invention has the following beneficial effects:

[0027] (1) The present invention separates and extracts platelet membranes, and co-extrudes them with nano-silica loading materials to obtain platelet membrane-coated nanoparticles (denoted as PM@MCS), which have good biosafety, biocompatibility and high targeting ability, and can effectively treat ALI.

[0028] (2) The present invention utilizes mesoporous silica to load two drugs, CeO2 nanozyme and sivelestat sodium. CeO2 nanozyme and sivelestat sodium work together to effectively inhibit the generation of NETs and enhance the ability to clear NETs, ​​thereby achieving the purpose of treating ALI.

[0029] (3) The present invention utilizes platelet membrane-coated nanoparticles to evade clearance by the immune system, achieve targeted drug delivery, and have good biosafety and biocompatibility. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The figures are the effect pictures of platelet membrane coated with nano-silica loading material, where A is an electron microscope picture, B is an SDS-PAGE electrophoresis picture, and C is a protein blotting picture.

[0031] Figure 2 These are the effect diagrams for verifying the safety of PM@MCS biological preparations in vivo and in vitro, where A is the in vitro safety effect diagram; B, C, D, E, F, G, and H are all in vivo safety effect diagrams.

[0032] Figure 3 Figure 1 is the effect of PM@MCS treatment on improving the prognosis of lung injury in mice, where A is the analysis of pathological sections in different groups after treatment, B is the comparison of serum pro-inflammatory cytokine levels in different groups after treatment, C is the weight change of mice in different groups after 7 days of treatment, and D is the survival rate change of mice in different groups after 7 days of treatment. I is the normal group, II is the PBS group, III is the SE group, IV is the CeO2 group, V is the MCS group, and VI is the PM@MCS group; *** P < 0.001, **** P < 0.0001. DETAILED DESCRIPTION

[0033] The present invention is further described in detail below through specific preferred embodiments, but the present invention is not limited to the following embodiments.

[0034] It should be noted that, unless otherwise specified, the chemical reagents involved in the present invention were purchased through commercial channels.

[0035] Example 1

[0036] A method for preparing platelet membrane-coated nanoparticles comprises the following steps:

[0037] S1. Preparation of mesoporous nano-silica: 2 g of hexadecyltrimethylammonium chloride and 0.02 g of triethylamine were added to 20 mL of deionized water and stirred evenly. Subsequently, 1.5 mL of mesitylene and 1.5 mL of ethyl orthosilicate were added and stirred for reaction at 95 °C for 1 h. Then, ethanol was refluxed at 80 °C for 8 h. After reflux three times, CTAC was removed and centrifuged. The resulting precipitate was mesoporous nano-silica (denoted as MSN).

[0038] S2. Preparation of cerium oxide: 0.43 g of cerium acetate and 3.25 g of oleylamine were added to 15 mL of xylene, stirred at room temperature for 20 h, then aged for 3 h under nitrogen protection, and cerium oxide (CeO2) was obtained by precipitation with acetone.

[0039] S3. Preparation of nano-silica loading material: disperse 1 g of mesoporous nano-silica and 1.5 g of cerium oxide in 20 mL of deionized water to obtain a dispersion; dissolve 4 g of sivelestat sodium in 20 mL of DMSO to obtain a sivelestat sodium solution, then add the sivelestat sodium solution to the dispersion, stir at 300 rpm for 24 h, and centrifuge at 10,000 rpm to obtain a precipitate, thereby obtaining a nano-silica loading material (denoted as MCS).

[0040] S4. Extraction of platelet membrane: Blood was collected from anesthetized BABL / c mice to obtain whole blood, which was centrifuged twice at 1050 rpm for 20 min each time to obtain platelet-rich plasma. Phosphate buffer containing 1 mM EDTA was added to inhibit platelet activation, followed by centrifugation at 300 rpm for 20 min, and platelet precipitates were collected. The blood was frozen and thawed repeatedly at -80°C for 5 times, and then centrifuged at 12000 g for 20 min to collect platelet membrane (PM) precipitates.

[0041] S5. Preparation of platelet membrane-coated nanoparticles: Add platelet membrane and nano-silica loading material into deionized water and mix evenly, wherein the concentration of platelet membrane is 1 mg / L, and the concentration of nano-silica loading material is 1 mg / L, and then treat under an ultrasonic power of 100 W for 5 minutes, and then use a liposome extruder to extrude it repeatedly 20 times to obtain platelet membrane-coated nanoparticles (denoted as PM@MCS).

[0042] Example 2

[0043] A method for preparing platelet membrane-coated nanoparticles comprises the following steps:

[0044] S1. Preparation of mesoporous nano-silica: 1.5 g hexadecyltrimethylammonium chloride and 0.01 g triethylamine were added to 20 mL deionized water and stirred evenly. Subsequently, 1 mL mesitylene and 1 mL ethyl orthosilicate were added and stirred for reaction at 95°C for 1 h. Then, ethanol was refluxed at 80°C for 8 h. After reflux three times, CTAC was removed and centrifuged. The resulting precipitate was mesoporous nano-silica (denoted as MSN).

[0045] S2. Preparation of cerium oxide: 0.43 g of cerium acetate and 3.25 g of oleylamine were added to 15 mL of xylene, stirred at room temperature for 20 h, then aged for 3 h under nitrogen protection, and cerium oxide (CeO2) was obtained by precipitation with acetone.

[0046] S3. Preparation of nano-silica loading material: disperse 1 g of mesoporous nano-silica and 1 g of cerium oxide in 20 mL of deionized water to obtain a dispersion; dissolve 3 g of sivelestat sodium in 20 mL of DMSO to obtain a sivelestat sodium solution, then add the sivelestat sodium solution to the dispersion, stir at 300 rpm for 24 h, and centrifuge at 10,000 rpm to obtain a precipitate, thereby obtaining a nano-silica loading material (denoted as MCS).

[0047] S4. Extraction of platelet membrane: Blood was collected from anesthetized BABL / c mice to obtain whole blood, which was centrifuged twice at 1050 rpm for 20 min each time to obtain platelet-rich plasma. Phosphate buffer containing 1 mM EDTA was added to inhibit platelet activation, followed by centrifugation at 300 rpm for 20 min, and platelet precipitates were collected. The blood was frozen and thawed repeatedly at -80°C for 5 times, and then centrifuged at 12000 g for 20 min to collect platelet membrane (PM) precipitates.

[0048] S5. Preparation of platelet membrane-coated nanoparticles: Add platelet membrane and nano-silica loading material into deionized water and mix evenly, wherein the concentration of platelet membrane is 1.5 mg / L, and the concentration of nano-silica loading material is 1 mg / L, and then treat under an ultrasonic power of 100 W for 5 minutes, and then use a liposome extruder to extrude it repeatedly 20 times to obtain platelet membrane-coated nanoparticles (denoted as PM@MCS).

[0049] Example 3

[0050] A method for preparing platelet membrane-coated nanoparticles comprises the following steps:

[0051] S1. Preparation of mesoporous nano-silica: Add 2.5 g of hexadecyltrimethylammonium chloride and 0.03 g of triethylamine to 20 mL of deionized water, stir evenly, then add 2 mL of mesitylene and 2 mL of ethyl orthosilicate, stir and react at 95°C for 1 h, then reflux in ethanol at 80°C for 8 h, reflux 3 times, remove CTAC, centrifuge, and the resulting precipitate is mesoporous nano-silica (denoted as MSN).

[0052] S2. Preparation of cerium oxide: 0.43 g of cerium acetate and 3.25 g of oleylamine were added to 15 mL of xylene, stirred at room temperature for 20 h, then aged for 3 h under nitrogen protection, and cerium oxide (CeO2) was obtained by precipitation with acetone.

[0053] S3. Preparation of nano-silica loading material: disperse 1 g of mesoporous nano-silica and 1 g of cerium oxide in 20 mL of deionized water to obtain a dispersion; dissolve 3 g of sivelestat sodium in 20 mL of DMSO to obtain a sivelestat sodium solution, then add the sivelestat sodium solution to the dispersion, stir at 300 rpm for 24 h, and centrifuge at 10,000 rpm to obtain a precipitate, thereby obtaining a nano-silica loading material (denoted as MCS).

[0054] S4. Extraction of platelet membrane: Blood was collected from anesthetized BABL / c mice to obtain whole blood, which was centrifuged twice at 1050 rpm for 20 min each time to obtain platelet-rich plasma. Phosphate buffer containing 1 mM EDTA was added to inhibit platelet activation, followed by centrifugation at 300 rpm for 20 min, and platelet precipitates were collected. The blood was frozen and thawed repeatedly at -80°C for 5 times, and then centrifuged at 12000 g for 20 min to collect platelet membrane (PM) precipitates.

[0055] S5. Preparation of platelet membrane-coated nanoparticles: Add platelet membrane and nano-silica loading material into deionized water and mix evenly, wherein the concentration of platelet membrane is 2 mg / L, and the concentration of nano-silica loading material is 1 mg / L, and then treat under an ultrasonic power of 100 W for 10 minutes, and then use a liposome extruder to extrude repeatedly 20 times to obtain platelet membrane-coated nanoparticles (denoted as PM@MCS).

[0056] Example 4

[0057] A method for preparing platelet membrane-coated nanoparticles comprises the following steps:

[0058] S1. Preparation of mesoporous nano-silica: Add 2.5 g of hexadecyltrimethylammonium chloride and 0.03 g of triethylamine to 20 mL of deionized water, stir evenly, then add 2 mL of mesitylene and 2 mL of ethyl orthosilicate, stir and react at 95°C for 1 h, then reflux in ethanol at 80°C for 8 h, reflux 3 times, remove CTAC, centrifuge, and the resulting precipitate is mesoporous nano-silica (denoted as MSN).

[0059] S2. Preparation of cerium oxide: 0.43 g of cerium acetate and 3.25 g of oleylamine were added to 15 mL of xylene, stirred at room temperature for 20 h, then aged for 3 h under nitrogen protection, and cerium oxide (CeO2) was obtained by precipitation with acetone.

[0060] S3. Preparation of nano-silica loading material: disperse 1 g of mesoporous nano-silica and 2 g of cerium oxide in 20 mL of deionized water to obtain a dispersion; dissolve 5 g of sivelestat sodium in 20 mL of DMSO to obtain a sivelestat sodium solution, then add the sivelestat sodium solution to the dispersion, stir at 300 rpm for 24 h, and centrifuge at 10,000 rpm to obtain a precipitate, thereby obtaining a nano-silica loading material (denoted as MCS).

[0061] S4. Extraction of platelet membrane: Blood was collected from anesthetized BABL / c mice to obtain whole blood, which was centrifuged twice at 1050 rpm for 20 min each time to obtain platelet-rich plasma. Phosphate buffer containing 1 mM EDTA was added to inhibit platelet activation, followed by centrifugation at 300 rpm for 20 min, and platelet precipitates were collected. The blood was frozen and thawed repeatedly at -80°C for 5 times, and then centrifuged at 12000 g for 20 min to collect platelet membrane (PM) precipitates.

[0062] S5. Preparation of platelet membrane-coated nanoparticles: Add platelet membrane and nano-silica loading material into deionized water and mix evenly, wherein the concentration of platelet membrane is 3 mg / L, and the concentration of nano-silica loading material is 1 mg / L, and then treat under an ultrasonic power of 100 W for 10 minutes, and then use a liposome extruder to extrude repeatedly 20 times to obtain platelet membrane-coated nanoparticles (denoted as PM@MCS).

[0063] The performance test of the platelet membrane-coated nanoparticles (PM@MCS) prepared in Example 1 of the present invention was carried out as follows:

[0064] Test Example 1 Evaluation of platelet membrane coating effect

[0065] Transmission electron microscopy was used to observe the morphology of mesoporous nanosilica (MSN), cerium oxide (CeO2), platelet membrane (PM) and PM@MCS. SDS-PAGE was used to verify the integrity of membrane extraction. Western blotting was used to detect PM and PM@MCS to confirm the expression of membrane-characteristic markers.

[0066] The test results are as follows Figure 1 As shown, from Figure 1 As can be seen in Figure A, the sizes of mesoporous nano-silica (MSN), cerium oxide (CeO2), and platelet membrane (PM) are nanoscale, and the nano-silica support material (MCS) is successfully coated by the platelet membrane (PM); Figure 1 B in the figure shows that the platelet membrane extracted by the present invention has a complete structure; Figure 1 Center C shows that the marker proteins on the platelet membrane surface are successfully expressed.

[0067] Experimental Example 2 Biosafety Assessment of PM@MCS

[0068] The present invention evaluates the safety of PM@MCS through in vitro cell experiments and in vivo animal experiments.

[0069] In vitro safety assessment: 3T3 cells were cultured at 5×10 3 / well were inoculated in a 96-well plate, and the cells were incubated with PM@MCS at different concentrations for 24 h and 48 h, respectively. The OD value of the cell supernatant at 450 nm was measured by CCK-8 method.

[0070] The test results are as follows Figure 2 As shown in Figure A, it can be seen that after 24 h and 48 h of incubation of PM@MCS with 3T3 cells, the cell survival rate reached more than 90%.

[0071] In vivo safety assessment: BABL / c mice were intraperitoneally injected with 30 mg / kg PM@MCS, with 3 mice in each group. Seven days after the injection, the main organs and serum were collected, and the pathological sections and blood biochemical indicators such as urea, creatinine, lactate dehydrogenase, alkaline phosphatase, aspartate aminotransferase, and alanine aminotransferase were measured.

[0072] Seven days after PM@MCS injection, compared with the normal group mice, Figure 2 As shown in B, C, D, E, F, and G, blood biochemical tests also showed normal ranges; Figure 2 As shown in H, there are no abnormalities in the heart, liver, spleen, lungs, and kidneys, and no obvious lesions.

[0073] The above in vitro and in vivo test results indicate that the PM@MCS prepared by the present invention is very safe and will not cause damage to the body.

[0074] Experimental Example 3 Testing of the therapeutic effect of PM@MCS on sepsis ALI

[0075] ALI was induced by cecal ligation and puncture (CLP) in 6-8 week old BABL / c mice. Six groups were set up to observe the experimental results, including normal group, PBS, sivelestat sodium (SE), CeO2 (prepared by step S2 of Example 1 of the present invention), MCS (prepared by step S3 of Example 1 of the present invention), and PM@MCS, with 5 mice in each group. The specific experimental steps of CLP are as follows: anesthetize the mice, shave the hair in the left lower abdomen, disinfect with iodine, make a small incision (about 1 cm), gently pull out the cecum with forceps, ligate 50% of the cecum with surgical sutures, puncture with a needle, squeeze out an appropriate amount of intestinal contents from the puncture site, put the cecum back into the abdominal cavity, and suture it. The mice were subcutaneously injected with pre-warmed 37°C sterile saline (1 mL) for fluid resuscitation. 12h after CLP, except for the normal group (normal mice) and PBS group (mice not given medicine after CLP), the SE group was intraperitoneally injected with 40mg / kg sivelestat sodium, the CeO2 group was injected with 15mg / kg CeO2, the MCS group was injected with 10mg / kg MCS, and the PM@MCS group was injected with 10mg / kg PM@MCS. The mice were killed 24h after administration, and the lung tissues were collected and pathological staining analysis was performed after being immersed in 4% formalin solution; whole blood and serum were collected to determine the proinflammatory cytokines TNF-α, IL-1β, and IL-6; the changes in mouse body weight and survival rate 7 days after administration were observed and recorded.

[0076] The results are as follows Figure 3 As shown in Figure A, pathological staining analysis showed that compared with the PBS group, the PM@MCS preparation group had significantly improved inflammatory infiltration and pulmonary edema in the lung tissue due to the targeting of the platelet membrane, evasion of immune system surveillance, and excellent biocompatibility. Figure 3 As shown in B, the determination of pro-inflammatory cytokines showed that the PM@MCS preparation group had the most significant decrease in inflammation; Figure 3 As shown in C and D, 7 days after administration, the PM@MCS group had the most significant increase in body weight and a higher survival rate.

[0077] The PM@MCS prepared by the present invention can significantly reduce the level of sepsis-related lung injury inflammation, improve pathological conditions, and prolong the survival rate of mice, thereby greatly improving the prognosis of ALI.

[0078] Finally, it should be noted that the above embodiments do not limit the present invention in any form. For those skilled in the art, some modifications and improvements can be made to the present invention. Therefore, any modification or improvement made without departing from the spirit of the present invention belongs to the scope of protection claimed in the present invention.

Claims

1. A method for preparing platelet membrane-coated nanoparticles, characterized in that: The steps include: S1, dispersing mesoporous nano-silica and cerium oxide in deionized water, then adding sivelestat sodium solution thereto, stirring and mixing evenly, and centrifuging to obtain a nano-silica supported material; S2, extracting and preparing platelet membrane from platelet-rich plasma; S3, adding the platelet membrane obtained in step S2 and the nano-silica loaded material obtained in step S1 into deionized water, mixing them evenly and then ultrasonically treating them, and then repeatedly extruding them 10-30 times using a liposome extruder to obtain platelet membrane-coated nanoparticles.

2. The preparation method according to claim 1, characterized in that: In step S1, the mass ratio of mesoporous nano-silica, cerium oxide and sivelestat sodium is 1:1-2:3-5.

3. The preparation method according to claim 1, characterized in that: In step S2, the specific process for extracting and preparing platelet membrane is as follows: blood is collected from anesthetized mice, and platelet-rich plasma is obtained by centrifugation, which is added to a phosphate buffer containing EDTA to inhibit platelet activation, followed by centrifugation to collect platelet precipitates, and the platelet membrane precipitates are collected after repeated freezing and thawing at -80°C and centrifugation.

4. The preparation method according to claim 1, characterized in that: In step S3, the mass ratio of the platelet membrane to the nano-silica supported material is 1-3:

1.

5. The preparation method according to claim 1, characterized in that: In step S3, the ultrasonic power is 100-200 W, and the ultrasonic time is 5-10 min.

6. Platelet membrane-coated nanoparticles prepared by the preparation method according to any one of claims 1 to 5.

7. Use of the platelet membrane-coated nanoparticles according to claim 6 in the preparation of a drug for treating sepsis-related acute lung injury.

8. The use according to claim 7, characterized in that: The dosage form of the drug is injection, tablet, capsule, granule, pill, oral solution or emulsion.

9. The use according to claim 7, characterized in that: The medicament also includes a pharmaceutically acceptable carrier.

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