Engineered cell membrane nanoparticles as well as preparation method and application thereof

Abstract

The invention relates to a bionic composite material and application thereof, the bionic composite material is an engineered cell membrane nanoparticle, the bionic composite material comprises a metal-polydopamine core and a biological coating, metal ions are chelated on the surface of a polydopamine nanoparticle to form the metal-polydopamine core, and the biological coating is coated on the surface of the metal-polydopamine core. The biological coating is a cell membrane extracted from macrophages which overexpress CXCR4, and the metal-polydopamine core is coated with the biological coating.

Description

Technical Field

[0001] The present application belongs to the field of biomimetic materials, and more specifically, relates to an engineered cell membrane nanoparticle and a preparation method and application thereof. Background Art

[0002] Cell membrane biomimetic materials, as an emerging drug delivery system, have made significant progress in recent years. By mimicking the structure and function of biological cell membranes, they can achieve precise drug delivery, improve drug efficacy, and reduce side effects. However, cell membrane biomimetic materials also suffer from insufficient targeting. Polydopamine nanoparticles, another emerging nanomaterial composed of polydopamine molecules, also have broad application prospects in the field of drug delivery. Polydopamine nanoparticles can be used as drug carriers, encapsulating drugs on the surface or inside the particles to achieve targeted drug delivery.

[0003] Although some researchers have tried to use cell membranes to wrap polydopamine nanoparticles to construct biomimetic materials, such materials also have problems such as insufficient targeting, uneven drug loading, and unstable drug release. Summary of the Invention

[0004] In one aspect of the present application, a biomimetic composite material is provided, comprising a metal-polydopamine core and a biocoating, wherein the metal is chelated in ionic form on the surface of polydopamine nanoparticles to form the metal-polydopamine core, the biocoating is a cell membrane extracted from macrophages overexpressing CXCR4, and the biocoating coats the metal-polydopamine core.

[0005] In some embodiments of the present application, the particle size of the polydopamine nanoparticles is 70 nm to 170 nm. In other embodiments of the present application, the particle size of the polydopamine nanoparticles is 90 nm to 130 nm. In some preferred embodiments of the present application, the average particle size of the polydopamine nanoparticles is 110 nm to 115 nm.

[0006] In some embodiments of the present application, the metal is a metal with a therapeutic effect. In some specific embodiments of the present application, the metal is strontium, gold or platinum. In some further embodiments of the present application, the metal is strontium and is chelated on the surface of the polydopamine nanoparticles in the form of strontium chloride.

[0007] In some embodiments of the present application, the polydopamine nanoparticles are nanoparticles formed by the following unit structures:

[0008]

[0009] The wavy lines represent the connecting bonds with adjacent unit structures.

[0010] In another aspect of the present application, a pharmaceutical composition is provided, comprising a biomimetic composite material and a pharmaceutically acceptable excipient, wherein the biomimetic composite material includes a metal-polydopamine core and a biocoating, wherein the metal is chelated in ionic form on the surface of polydopamine nanoparticles to form the metal-polydopamine core, the biocoating is a cell membrane extracted from macrophages overexpressing CXCR4, and the biocoating coats the metal-polydopamine core.

[0011] In some embodiments of the present application, the particle size of the polydopamine nanoparticles is 70 nm to 170 nm. In other embodiments of the present application, the particle size of the polydopamine nanoparticles is 90 nm to 130 nm. In some preferred embodiments of the present application, the average particle size of the polydopamine nanoparticles is 110 nm to 115 nm.

[0012] In some embodiments of the present application, the metal is a metal with a therapeutic effect. In some specific embodiments of the present application, the metal is strontium, gold or platinum. In some further embodiments of the present application, the metal is strontium and is chelated on the surface of the polydopamine nanoparticles in the form of strontium chloride.

[0013] In some embodiments of the present application, the polydopamine nanoparticles are nanoparticles formed by the following unit structures:

[0014]

[0015] The wavy lines represent the connecting bonds with adjacent unit structures.

[0016] In some embodiments of the present application, the pharmaceutically acceptable excipients include a binder, a diluent, a disintegrant, a lubricant, a glidant, a sweetener or a flavoring agent.

[0017] In another aspect of the present application, there is provided a use of a biomimetic composite material in the preparation of a drug for preventing or treating ischemic hypoxic diseases or injuries, wherein the biomimetic composite material comprises a strontium-polydopamine core and a biocoating, wherein the strontium-polydopamine core is formed by chelating strontium ions on the surface of polydopamine nanoparticles, the biocoating is a cell membrane extracted from macrophages overexpressing CXCR4, and the biocoating coats the metal-polydopamine core.

[0018] In some embodiments of the present application, the particle size of the polydopamine nanoparticles is 70 nm to 170 nm. In other embodiments of the present application, the particle size of the polydopamine nanoparticles is 90 nm to 130 nm. In some preferred embodiments of the present application, the average particle size of the polydopamine nanoparticles is 110 nm to 115 nm.

[0019] In some embodiments of the present application, strontium is chelated on the surface of the polydopamine nanoparticles in the form of strontium chloride. In some further embodiments of the present application, the polydopamine nanoparticles are nanoparticles formed from the following unit structures:

[0020]

[0021] The wavy lines represent the connecting bonds with adjacent unit structures.

[0022] In some embodiments, the hypoxic-ischemic disease is cardiac ischemia, cerebral ischemia, visceral ischemia, or limb ischemia. In some embodiments, the hypoxic-ischemic disease is myocardial infarction or stroke.

[0023] This application chelates metal ions such as strontium onto the surface of polydopamine nanoparticles to construct nanoparticles with therapeutic effects, and then uses cell membranes extracted from macrophages overexpressing CXCR4 to coat such nanoparticles, thereby obtaining novel biomimetic composite materials. Such materials not only have excellent targeting, but can also controllably release metal ions such as strontium, providing long-lasting and stable therapeutic effects. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The drawings provided below are intended to more clearly illustrate the embodiments of the present application, and it should be understood that the drawings are only some specific examples of the present application, which are intended to explain and illustrate the embodiments of the present application, and are not intended to limit the scope of protection of the present application.

[0025] Figure 1 A schematic diagram showing the technical route of this application.

[0026] Figure 2 Shown is a Western blot analysis according to one embodiment of the present application.

[0027] Figure 3 FIG2 shows fluorescence imaging of macrophages overexpressing CXCR4 according to one embodiment of the present application.

[0028] Figure 4 An infrared spectrum of polydopamine nanoparticles according to one embodiment of the present application is shown.

[0029] Figure 5A scanning electron microscope image of polydopamine nanoparticles according to one embodiment of the present application is shown.

[0030] Figure 6 A graph showing the particle size distribution of polydopamine nanoparticles according to one embodiment of the present application is shown.

[0031] Figure 7 Shown is an EDS spectrum analysis of a strontium-polydopamine core according to one embodiment of the present application.

[0032] Figure 8 Shown is the zeta potential analysis of the biomimetic composite material according to one embodiment of the present application.

[0033] Figure 9 The blood compatibility analysis of the biomimetic composite material according to one embodiment of the present application is shown.

[0034] Figure 10 The cytotoxicity analysis of the biomimetic composite material according to one embodiment of the present application is shown. DETAILED DESCRIPTION

[0035] To make the purpose, technical solutions, and technical benefits of this application more clear, the technical solutions of this application are described in detail below. The specific embodiments described are only some examples of this application, and are not exhaustive. Based on the embodiments in this application, all other implementation methods obtained by ordinary technicians in this field without making any creative efforts fall within the scope of protection of this application.

[0036] The inventors of this application first constructed membrane vesicles of macrophages overexpressing CXCR4. They then mixed and reacted strontium chloride with polydopamine nanoparticles, chelating the strontium ions onto the surface of the polydopamine nanoparticles. Finally, they used a liposome extruder to repeatedly extrude the mixture of membrane vesicles and nanoparticles through membranes of varying pore sizes, thereby coating the surface of the nanoparticles with cell membranes extracted from CXCR4-overexpressing macrophages. Based on this, the inventors obtained a biomimetic nanocomposite material with excellent targeting properties, completing the invention disclosed herein.

[0037] Specifically, the biomimetic composite material of the present application includes a metal-polydopamine core and a biocoating, wherein the metal is chelated on the surface of polydopamine nanoparticles in the form of ions to form the metal-polydopamine core, the biocoating is a cell membrane extracted from macrophages overexpressing CXCR4, and the biocoating coats the metal-polydopamine core.

[0038] CXCR4 is a homologous receptor for stromal-derived factor-1 (SDF-1), a chemotactic factor required for progenitor cells to home to ischemic tissue. SDF-1 plays an important role in promoting cell homing to ischemic / hypoxic myocardium by recruiting progenitor cells expressing its homologous receptor CXCR4. SDF-1 expression is upregulated in myocardial tissue after infarction, and myocardial SDF-1 gene transfer increases the migration and homing of stem cells to ischemic myocardium. The interaction between SDF-1 and CXCR4, which are highly expressed in an ischemic environment, can improve the therapeutic efficacy of the biomimetic composite material of the present application. In some embodiments, CXCR4 is of human or mouse origin. The amino acid or encoding nucleic acid sequence of CXCR4 can be obtained by those skilled in the art through websites such as GenBank (e.g., GenBank No.NM_022205.3) or scientific literature.

[0039] In some embodiments, the polydopamine nanoparticles are nanoparticles formed from the following unit structures and have a particle size of 70 nm to 170 nm, for example, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140 nm, 150 nm, or 160 nm, or any sub-range within the range formed by these values, for example, 95 nm, 105 nm, 115 nm, or 125 nm. Preferably, the average particle size of the polydopamine nanoparticles is 110 nm to 115 nm, for example, 111 nm, 112 nm, 113 nm, or 114 nm.

[0040]

[0041] In the above structural formula, the wavy line represents the connection bond with the adjacent unit structure.

[0042] In some embodiments, the metal is strontium. Strontium is a trace element that has been shown to promote angiogenesis and increase vascularization. Chelating strontium onto polydopamine nanoparticles enhances the angiogenic effects of polydopamine nanoparticles while providing anti-inflammatory and antioxidant benefits.

[0043] In addition to strontium, other metals and / or metal ions with therapeutic effects can also be chelated onto the polydopamine nanoparticles, for example, gold or gold ions, platinum or platinum ions can be used.

[0044] In further embodiments, the biomimetic composite materials described herein can be formulated into pharmaceutical compositions with pharmaceutically acceptable excipients, or directly formulated into medicaments. Suitable excipients include, but are not limited to, binders, diluents, disintegrants, lubricants, glidants, sweeteners, or flavoring agents. Those skilled in the art may also employ any other adjuvants compatible with the biomimetic composite materials described herein.

[0045] According to the above introduction to CXCR4, the biomimetic composite material described herein is particularly suitable for preventing or treating ischemic hypoxic diseases or injuries. Specifically, ischemic hypoxic diseases can be cardiac ischemia (e.g., myocardial infarction), cerebral ischemia (e.g., stroke), visceral ischemia, or limb ischemia. During treatment, the biomimetic composite material herein can be formulated into an injection or oral solution, so that it can be administered by injection or oral administration. Of course, those skilled in the art can also adopt other modes of administration according to factors such as dosage, patient condition, etc.

[0046] This application uses lentivirus to construct and engineer CXCR4-overexpressing macrophages that target hypoxic-ischemic tissues, enhancing specific targeting through macrophage "receptor-ligand" interactions. Specifically, by coating the membranes of CXCR4-overexpressing macrophages with polydopamine nanoparticles chelated with metal ions such as strontium, while ensuring the efficacy of the therapeutic metal element, it also provides long-term circulation and targeted delivery capabilities, thereby enabling effective and long-lasting treatment of related diseases in vivo.

[0047] Example

[0048] The experimental materials used in the examples of this application are all conventional experimental materials in the field and can be purchased through commercial channels. Unless otherwise specified, all operations are conventional operations in the field and are carried out at room temperature and atmospheric pressure.

[0049] Example 1: Preparation of biomimetic composite materials

[0050] Example 1-1: Preparation of biocoating

[0051] Preparation of macrophages overexpressing CRCR4: Based on the coding sequence of CRCR4 shown in GenBank No. NM_022205.3, we commissioned a company to prepare a lentiviral-packaged CRCR4 expression vector, and through cell transfection and screening of macrophages (RAW264.7), we obtained a macrophage cell line stably expressing CRCR4. Figure 2 and Figure 3 As shown, Figure 2 It showed that the expression level of CXCR4 in macrophages transfected with CXCR4 plasmid was significantly increased. Figure 3 The results of fluorescence imaging also confirmed that CXCR4-overexpressing macrophages were successfully constructed.

[0052] Cell sample collection: low speed centrifugation (500-600×g, 5 minutes) to collect 2×10 7 The previously obtained macrophage cell line stably expressing CRCR4 (in this embodiment, there are approximately 1×10 7) cells. For adherent cells, use a cell scraper instead of trypsin. Then, wash the cells once with pre-cooled PBS, centrifuge (500-600×g, 5 minutes), completely remove the supernatant, and add 500ul Buffer A (Kit, Minute TM Resuspend the cells and incubate on ice for 5-10 minutes. Vortex vigorously for 10-30 seconds to ensure the cells are resuspended. Quickly transfer the cell suspension into a centrifuge column. Centrifuge at 16,000 × g for 30 seconds in a benchtop centrifuge. Discard the centrifuge column and vortex vigorously for 10 seconds to resuspend the pellet in the receiving tube.

[0053] The cells were separated into four components, namely, nucleus, cytoplasm, organelles and plasma membrane, by the following steps: 700 × g, centrifugation for 1 minute (wherein the precipitate is the intact nucleus and a small portion of unbroken intact cells), the supernatant was transferred to a new 1.5 mL centrifuge tube, and centrifuged at 16,000 × g for 10-30 minutes at 4°C, the supernatant was discarded (wherein the supernatant is the cytoplasm component), and the precipitate was saved (wherein the precipitate is the total membrane component, including organelles and plasma membrane). The total membrane yield is generally 10-500 ug / sample.

[0054] Add 200 μL of Buffer B (kit) and resuspend the total membrane fraction by pipetting or vortexing repeatedly. Centrifuge at 7,800 × g for 5 minutes at 4°C. The pellet represents the organelles. Carefully transfer the supernatant to a new 2.0 mL centrifuge tube and add 1.6 mL of pre-chilled PBS. Invert several times to mix. Centrifuge at 16,000 × g for 30 minutes. Discard the supernatant. The pellet represents the plasma membrane fraction. Resuspend the plasma membranes in each tube in 100 μL of PBS and freeze at -80°C.

[0055] Example 1-2: Preparation of Strontium-Polydopamine Nanoparticles

[0056] Polydopamine was synthesized according to the following system:

[0057] name 500ml system Tris-Base (Tris(hydroxymethyl)aminomethane) 0.6057g Anhydrous ethanol 83.3ml Ultrapure water 416.7ml Dopamine hydrochloride (DA) 0.5g

[0058] At room temperature, the above components were placed on a magnetic stirrer and stirred for 72 hours to react, and then dialyzed in a dialysis bag to remove salt. The synthesis process of polydopamine nanoparticles is shown below.

[0059]

[0060] Then, add an appropriate amount of dialysate (i.e., deionized water) to the dialysis apparatus (2L glass beaker). The volume of dialysate should be 100 times the sample volume. Cut 15-20 cm of dialysis tubing, leaving an extra length (approximately 20% of the total sample volume) as head space. Insert the dialysis tubing into the open dialysis clamp and clamp it at a position approximately 3-5 mm beyond the dialysis clamp. The dialysis bag must not be folded. Load the sample from the open end of the dialysis tubing, adjust the length of the head space, leaving 10-20%, and clamp the dialysis clamp. Place the dialyzed sample in dialysis buffer and dialyze overnight. Change the dialysate 2-4 hours, 6-8 hours, and 10-14 hours after dialysis. Continue dialysis for at least 2 hours after the last change of dialysate.

[0061] Pour the dialyzed polydopamine (PDA) into a culture dish, keeping the volume at half the dish, and freeze the dish at -80°C. Remove the lid of the dish that has been frozen overnight, cover it with plastic wrap, and poke holes in it with small scissors. Place the dish in a pre-chilled freeze dryer, close the cold well lid, and start dialysis until all water is frozen away.

[0062] like Figure 4 As shown, infrared spectroscopy shows the stretching of the CO bonds in the indole structure and the phenolic hydroxyl structure, proving the synthesis of polydopamine nanoparticles. Figure 5 The scanning electron micrograph shown shows polydopamine nanoparticles, Figure 6 The results show that the particle size distribution of the nanoparticles is relatively uniform, with an average particle size of 114 nm, and they have the potential to function as a carrier.

[0063] Strontium-polydopamine nanoparticles (hereinafter referred to as PDA-Sr) were synthesized as follows: ddH2O was added to PDA powder to prepare 1 mg / ml; 10 mg / ml strontium chloride aqueous solution was prepared; 1 mL of PDA solution was added to 20 μL of strontium chloride aqueous solution and reacted at 40°C for 1 hour; centrifuged at 15,000 rpm for 15 minutes and discarded the supernatant; washed twice with water and centrifuged at 15,000 rpm for 15 minutes each time; and freeze-dried. Strontium ions were modified on the surface of polydopamine nanoparticles through a chelation reaction and Figure 7 The energy spectrum analysis shown shows that strontium ions are successfully bound to the surface of polydopamine.

[0064] Examples 1-3: Preparation of biomimetic composite materials

[0065] The biomimetic nanomaterials were prepared by co-extrusion of cell membranes extracted from CXCR4-overexpressing macrophages onto the PDA-Sr surface using an Avanti Polar Lipids liposome extruder. 8A solution of cell membrane microcapsules extracted from 10 macrophages was thoroughly mixed with a 1mg PDA-Sr aqueous solution (1mg / ml). The mixture was sonicated at 42kHz and 100W for 2 minutes. The mixture was then extruded 7-10 times through a 200nm polycarbonate porous membrane using a liposome microextruder. The resulting biomimetic nanoparticle solution was collected and stored at 4°C until needed.

[0066] pass Figure 8 The zeta potential analysis shown in the figure shows that the electronegativity of PDA-Sr increases with the coating of macrophage membrane, and is close to the electronegativity of the cell membrane itself, which indicates that the cell membrane is successfully coated on PDA-Sr.

[0067] Example 2: In vitro blood testing of biomimetic composite materials

[0068] Strontium-polydopamine nanoparticles (PDA-Sr@CM, prepared as described in Example 1) coated with cell membranes extracted from macrophages overexpressing CXCR4 were mixed with blood, and water, PBS, and uncoated PDA-Sr were used as controls. This experiment showed that PDA-Sr@CM can coexist with blood for a long time without causing blood cell rupture, and has good blood compatibility. Figure 9 shown.

[0069] Example 3: Rat simulation evaluation of biomimetic composite materials

[0070] Primary cardiomyocytes (CMs) were isolated from the hearts of 0-1 day old newborn SD rats using the following method:

[0071] Newborn SD rats were anesthetized with isoflurane and disinfected twice with 75% alcohol. The chest cavity was opened with ophthalmic scissors, and the heart was quickly removed from the root of the rat's aorta. The heart was washed in sterile PBS at 4°C to remove blood. The blood vessels, pericardium, and atrium were carefully removed using ophthalmic forceps, and the remaining part was minced with ophthalmic scissors. The minced heart tissue was digested into a single-cell suspension using 0.05% trypsin, with each digestion lasting 3 minutes for 5 to 8 times. The single-cell suspension obtained by digestion was collected in H-DMEM medium containing 15% fetal bovine serum to terminate the digestion. The tube was centrifuged at 1200 rpm for 5 minutes, the supernatant was discarded, and the cells at the bottom of the centrifuge tube were collected. The cells were resuspended in 10 mL of H-DMEM medium containing 15% fetal bovine serum, pre-plated in a 10 cm culture dish, and incubated in an incubator for 3 hours. Taking advantage of the fact that fibroblasts adhere to the wall before CM, non-adherent CM was collected after 3 hours, resuspended after centrifugation, and inoculated into a 96-well plate. The density was such that each heart corresponded to 16 wells of the 96-well plate. The plate was cultured in a 37°C constant temperature incubator, and the culture medium was replaced every 2-3 days.

[0072] 3-1: CCK-8 detection of cell activity:

[0073] After CM was inoculated into a 96-well plate, the cells were treated with the biomimetic composite material obtained in Example 1 at the following concentrations: control group (no biomimetic composite material added), 50 μg / ml, 100 μg / ml, 200 μg / ml, 400 μg / ml, 800 μg / ml, and 1600 μg / ml for treating cardiomyocytes. After 1 day of culture, the culture medium was discarded and 100 μL / well CCK-8 working solution (H-DMEM culture medium: stock solution = 100:1) was added. After incubation in a 37°C constant temperature incubator in the dark for 1 hour, 100 μL of the solution per well was transferred to a new 96-well plate and the absorbance at 450 nm was measured using a microplate reader. The cell viability of each group was calculated by dividing the absorbance of that group by the absorbance of the control group.

[0074] The results showed that PDA was significantly toxic at a concentration of 400 μg / ml, while PDA-Sr and PDA-Sr@CM were cytotoxic at 200 μg / ml. Figure 10 shown.

[0075] 3-2: Effects on primary cardiomyocyte maturation and biomarker expression:

[0076] Primary CMs were seeded into 24-well plates containing slides at the same seeding density as above. After 3 days, the medium was changed and PDA, PDA-Sr, and PDA-Sr@CM were added at the same concentrations as above. After 24 hours of incubation, the medium was washed away and the cells were treated with 4% paraformaldehyde for 12 hours, 1% Triton X-100 for 30 minutes, and goat serum blocking buffer for 2 hours. Subsequently, the cells were incubated with antibodies. Primary antibodies for c-TnT and Cx-43 were prepared at dilutions of 1:200 and 1:500, respectively. Secondary antibodies for Cy3-conjugated goat anti-rabbit Alex488 and Alex568-conjugated goat anti-mouse IgG were prepared at dilutions of 1:1000 and 1:500, respectively. CMs were then double-stained for c-TnT and Cx-43 proteins. The samples were incubated with the primary antibody working solution at 4°C overnight, washed three times with PBS, and then incubated with the secondary antibody working solution at 37°C for 30 minutes. After washing three times with PBS, the samples were stained for cell nuclei and mounted with anti-fluorescence quenching mounting medium, and photographed using a confocal microscope.

[0077] Results: PDA, PDA-Sr and PDA-Sr@CM groups showed the ability to promote cardiomyocyte maturation and express more cardiomyocyte marker proteins, among which the PDA-Sr@CM group showed a more significant effect.

[0078] 3-3: Effects on the evaluation of antioxidant capacity of neonatal rat primary cardiomyocytes:

[0079] CMs were treated with PDA, PDA-Sr, and PDA-Sr@CM at the aforementioned concentrations for 3 days. Fluorescent probe dyes DCFH-DA and DHE were diluted in PBS to a 1% dilution. This solution was then used to replace the CM medium. After an additional 30-minute incubation, fluorescence imaging was performed using UV and blue light excitation, and antioxidant capacity was assessed.

[0080] Results: The PDA, PDA-Sr, and PDA-Sr@CM groups exhibited significant antioxidant function, with the PDA-Sr@CM group showing a more significant effect.

[0081] Example 4: Mouse model test of biomimetic composite materials

[0082] After myocardial ischemia, an environment with high expression of stromal cell-derived factor 1 (SDF-1) and inflammatory factors (TNF-α, IL-1β, and IL-6) is created. Overexpression of CXCR4, a receptor for SDF-1, on the membranes of macrophages, which sequester these inflammatory factors, is specifically targeted. The anticipated result is that PDA-Sr@CM exhibits therapeutic effects (such as promoting angiogenesis), while maintaining the efficacy of functional nanomaterials while also providing long-term circulation and targeted delivery capabilities.

[0083] The above description is merely a specific embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications or substitutions that can be easily conceived by a person skilled in the art within the technical scope disclosed in the present invention should be included in the scope of protection of the present invention. Therefore, the scope of protection of the present invention should be based on the scope of protection of the claims.

Claims

1. A biomimetic composite material comprising a metal-polydopamine core and a biocoating, wherein the metal is chelated in ionic form on the surface of polydopamine nanoparticles to form the metal-polydopamine core, the biocoating is a cell membrane extracted from macrophages overexpressing CXCR4, and the biocoating coats the metal-polydopamine core. 2 . The biomimetic composite material according to claim 1 , wherein the particle size of the polydopamine nanoparticles is 70 nm to 170 nm, for example, 90 nm to 130 nm. Preferably, the average particle size of the polydopamine nanoparticles is 110 nm to 115 nm. 3 . The biomimetic composite material according to claim 1 , wherein the metal is a metal with therapeutic effects, such as strontium, gold or platinum. Preferably, the metal is strontium and is chelated on the surface of the polydopamine nanoparticles in the form of strontium chloride.

4. The biomimetic composite material according to any one of claims 1 to 4, wherein the polydopamine nanoparticles are nanoparticles formed by the following unit structure: in, The wavy lines represent the bonds to adjacent unit structures.

5. A pharmaceutical composition comprising a biomimetic composite material and a pharmaceutically acceptable excipient, wherein the biomimetic composite material includes a metal-polydopamine core and a biocoat, wherein the metal is chelated in ionic form on the surface of polydopamine nanoparticles to form the metal-polydopamine core, and the biocoat is a cell membrane extracted from macrophages overexpressing CXCR4, and the biocoat coats the metal-polydopamine core.

6. The pharmaceutical composition according to claim 5, wherein the pharmaceutically acceptable excipient comprises a binder, a diluent, a disintegrant, a lubricant, a glidant, a sweetener or a flavoring agent.

7. The pharmaceutical composition according to claim 5, wherein the metal is a metal having therapeutic effects, such as strontium, gold or platinum, and / or The average particle size of the polydopamine nanoparticles is 110 nm to 115 nm, and the nanoparticles are formed by the following unit structure: in, The wavy lines represent the bonds to adjacent unit structures.

8. Use of a biomimetic composite material in preparing a medicament for preventing or treating ischemic hypoxic diseases or injuries, wherein the biomimetic composite material comprises a strontium-polydopamine core and a biocoat, wherein the strontium-polydopamine core is formed by chelating strontium ions on the surface of polydopamine nanoparticles, the biocoat is a cell membrane extracted from macrophages overexpressing CXCR4, and the biocoat coats the metal-polydopamine core.

9. The use according to claim 8, wherein the ischemic-hypoxic disease is cardiac ischemia such as myocardial infarction, cerebral ischemia such as stroke, visceral ischemia or limb ischemia.

10. The use according to claim 8, wherein the strontium is chelated on the surface of the polydopamine nanoparticles in the form of strontium chloride, and / or The average particle size of the polydopamine nanoparticles is 110 nm to 115 nm, and the nanoparticles are formed by the following unit structure: in, The wavy lines represent the bonds to adjacent unit structures.

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