CN115581684B - Manufacturing method and application of macrophage membrane-coated hair nano particles - Google Patents
Manufacturing method and application of macrophage membrane-coated hair nano particles Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/5176—Compounds of unknown constitution, e.g. material from plants or animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/12—Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
- A61K35/36—Skin; Hair; Nails; Sebaceous glands; Cerumen; Epidermis; Epithelial cells; Keratinocytes; Langerhans cells; Ectodermal cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y40/00—Manufacture or treatment of nanostructures
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B82—NANOTECHNOLOGY
- B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
- B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
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- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Crystallography & Structural Chemistry (AREA)
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- General Chemical & Material Sciences (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Cell Biology (AREA)
- Dermatology (AREA)
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Abstract
The invention discloses a preparation method and application of macrophage membrane-coated hair nano particles, wherein the preparation method comprises the steps of taking black hair of a human body as a raw material, preparing the hair nano particles by an alkali extraction method, and treating diabetes foot ulcer with infection due to the fact that main constituent substances of the hair nano particles are melanin and keratin which are sensitive to photothermal treatment. The macrophage membrane is prepared by the extrusion method, and the hair nano particles are wrapped in the macrophage membrane by the ultrasonic fusion method, so that the adhesion force and the adhesion efficiency of the hair nano particles to bacteria in an infected area can be effectively enhanced, and the biocompatibility is high. Compared with the prior art and nano particles, the hair nano particles wrapped by macrophage membranes are all derived from the living bodies of human bodies or mice, are produced from natural biological materials, have the characteristics of environment friendliness, low cost, simple preparation, low toxicity and the like, have obvious curative effect on the treatment of diabetic foot ulcer infection and have good application prospect on the treatment dilemma of diabetic foot ulcer infection.
Description
Technical Field
The invention relates to the field of biomedical materials, in particular to a preparation method and application of macrophage membrane-coated hair nano particles.
Background
The prevalence of global diabetic foot ulcers is 6.3%, with type 2 diabetes being higher than type 1 diabetes, and the proportion of men being higher than women. Foot ulcers are the most common manifestation of diabetic foot disease and are also the leading cause of amputation in diabetics. In China, the annual incidence rate of diabetic foot ulcers is 8.1%, the annual death rate is 14.4%, and the annual recurrence rate is as high as 31.6%. Diabetic foot disease is very poorly predicted and even more frequently than the mortality and disability rate of most cancers. Diabetic Foot Infection (DFI) is one of the most important causes of exacerbation, amputation and death in diabetic foot patients. In terms of severity, nearly half of patients were Wagner grade 3 or more lesions (moderately severe lesions), with a total amputation rate of about 20%. Among them, wagner 1 patients had gram-positive cocci with an infection rate as high as approximately 100% and staphylococcus aureus infections of approximately 60%. The current treatment principle is that when abscess appears, the whole body is treated by using antibacterial drugs, and local debridement drainage and dressing replacement are combined in time. Considering that the DFI patient has poor local microcirculation, the systemic antibiotic treatment reaches the lower blood concentration of the wound site and cannot replace the thorough wound debridement treatment, but the local application of the antibiotic can break the balance of the wound microenvironment, cause the increase of the drug resistance of sensitive bacteria and break the balance of the wound microenvironment so as to influence the tissue regeneration and repair.
Types of topical dressings in common use today include: hydrocolloid-based dressing, hydrogel-based dressing, alginate-based dressing, foam-based dressing, silver ion dressing, and the like. Hydrocolloid or hydrogel dressing is generally selected when exudation is high, silver ion dressing is generally selected when infection is heavy, and the dressing change frequency is 1-3 days until fresh granulation of the wound surface is formed. Antibacterial dressing including silver ion dressing, honey dressing, SUYULE callus dressing, etc. At present, the characteristics of broad-spectrum bacteriostasis of silver ions are considered, the action time is long, drug resistance is not easy to generate, but recent animal experiments show that the silver ion dressing is more suitable for healing of ulcers and infection of common mice, and can promote healing of diabetic mice but can not obviously reduce bacterial load, so that whether the silver ion dressing is an optimal DFI dressing is still to be clarified. The photothermal treatment can convert absorbed light energy into heat energy by using a photothermal reagent, and is a novel non-antibiotic mode for targeted killing of bacteria. Because melanin has good photo-thermal conversion performance and excellent biocompatibility, the melanin can be prepared into novel antibacterial materials.
Studies have shown that by exploiting the feature that inflamed endothelial cells up-regulate the expression of vascular cell adhesion molecule-1 (VCAM-1) to recruit immune cells, genetically engineered extraction of cell membranes over-expressing VCAM-1 and exploiting the specific affinity between very late antigen-4 (VLA-4) and VCAM-1 results in biomimetic nanoparticle formulations capable of targeting inflammation. Considering that macrophages are inflammatory initiating cells of infection, it would be a great advantage if the membrane coating of macrophages was used to encapsulate antibacterial drugs, which would have great potential in wound treatment of DFI.
Disclosure of Invention
The invention aims to solve the problems of low local drug concentration and poor treatment effect of the traditional DFI, and provides a preparation method and application of a macrophage membrane-coated hair nanoparticle.
In order to achieve the above purpose, the technical scheme provided by the invention is as follows: a method for preparing hair nano-particles coated by macrophage membrane comprises preparing hair nano-particles from human hair by alkali extraction method, squeezing to obtain macrophage membrane, and ultrasonic fusing to obtain hair nano-particles coated by macrophage membrane.
Further, in mass ratio 2:1, fusing the hair nano-particles and the macrophage membrane according to the proportion, and wrapping the hair nano-particles in the macrophage membrane by using ultrasonic water bath.
Further, the ultrasonic water bath condition is 220W, and the ice water bath is carried out for 20 minutes.
Further, the particle size of the hair nanoparticle and macrophage membrane is less than 100nm.
Further, the preparation process of the hair nanoparticle comprises the following steps: adding human hair into the heated alkaline solution, stirring until the hair is completely dissolved, and sequentially performing dialysis, stirring, centrifugation, drying by distillation and ultrasound to obtain the hair nano-particles.
Further, the temperature of the heated alkaline solution is 80 ℃, the alkaline solution is NaOH solution, and the stirring time is 5 minutes; dialysis conditions were 7000kD molecular weight cut-off, dialysis in 1 XPBS solution for 24 hours; stirring is carried out for 1.5 hours at room temperature in a magnetic stirrer at a rotating speed of 100 rpm/min; centrifuging at 2000rpm/min for 6 min, collecting supernatant, centrifuging at 12000rpm/min for 10 min, collecting black precipitate, and adding ddH 2 Repeating the centrifugation at 12000rpm/min for 2 times after the O solution is washed; the ultrasonic condition is that the hair micron particles are crushed for 1 hour in an ice-water bath by using an ultrasonic probe with 520W power, and the condition is that the ultrasonic is started for 3 seconds and stopped for 1 second.
Further, the preparation process of the macrophage membrane comprises the following steps: culturing a mouse macrophage line RAW 264.7, and obtaining cell sediment after digestion; cell pellet was lysed with RIPA lysate (strong) on ice containing 1mM phenylmethylsulfonyl fluoride (PMSF), followed by shaking the solution in an ice water bath with a 45W power ultrasonic probe; centrifuging the ultrasonic solution at 4 ℃, and taking and preserving the supernatant; adding the obtained supernatant into RIPA lysate (strong) containing 1mM PMSF, sending into an overspeed centrifuge tube, discarding the supernatant after ultracentrifugation, retaining the precipitate, and blowing with 1 XPBS to homogenize the precipitate to obtain macrophage membrane solution; continuously extruding and pushing the macrophage membrane solution by an Avantis extruding and pushing device to obtain the macrophage membrane solution (RAWM) in a vesicle form, and quantifying protein to determine the concentration of the solution.
Further, the solution is crushed for 30 minutes in an ice-water bath by using an ultrasonic probe with power of 45W, and the condition is that the ultrasonic is started for 2 seconds and stopped for 3 seconds; centrifuging at 20000rpm/min for 20 min to remove cell nucleus; ultracentrifugation conditions were 100000g/min, centrifugation at 4℃for 45 min; the squeezing aperture of the Avantis squeezing device is 400nm, and the squeezing times are 11 times.
In a second aspect, the present invention also provides a macrophage membrane-coated hair nanoparticle prepared based on the above method.
In a third aspect, the invention also provides application of the macrophage membrane-coated hair nanoparticle in preparing a medicament for treating diabetic foot ulcer infection.
Compared with the prior art, the invention has the beneficial effects that:
(1) According to the invention, the HNP is coated by the RAWM, so that the adhesion between the RAWM and epidermal cells can be better increased due to the high expression of the integrin alpha 4 by the RAWM, and the bacteria are pulled, so that more HNP can be adhered to inflammatory infection parts; and HNP contains a large amount of melanin, so that the HNP has the characteristics of good photo-thermal effect and capability of being heated after being excited by laser, and the HNP is irradiated to the temperature of the skin to 50 ℃ by using a 808nm laser, and the HNP is maintained for 5 minutes to kill bacteria and promote healing of infected ulcers. The preparation method has the advantages of simple preparation flow, low cost of raw materials, convenient mass production, natural components, good biocompatibility compared with inorganic nano materials and the like, and higher biological safety.
(2) The invention cultures the bacterial liquid of the DFI patient to the wound surface of the diabetic ulcer mouse, and simulates the treatment in human body. From the aspect of treatment effect, the invention not only can promote ulcer healing, but also has obvious antibacterial effect and has expected clinical application value.
(3) The RAWM liposome carrier prepared by the invention can be used for the application of personalized in-vivo exogenous infection focus, and has wide clinical application prospect.
Drawings
Fig. 1 is a schematic representation of the preparation process of Hair Nanoparticle (HNP) and macrophage membrane (RAWM) of the present invention.
FIG. 2 is a schematic diagram of a transmission electron microscope of the present invention, wherein A-C are transmission electron microscope images of HNP, RAWM and HNP@RAWM, respectively.
Fig. 3 is a statistical diagram of particle size and potential values according to the present invention, wherein a is the average particle size of HNP, RAWM and hnp@rawm, and B is a statistical diagram of Zeta potential values.
FIG. 4 is a schematic diagram of protein components and protein expression abundance, wherein A is a protein component expressed by macrophage characteristics contained on the surface of RAWM, and B is identification of protein expression abundance after HNP@RAWM is prepared.
Fig. 5 is a graph showing that hnp@rawm increases HNP adhesion to staphylococcus aureus compared to HNP (scale = 1 μm).
Fig. 6 is a schematic diagram showing the results of in vitro experiments, wherein a represents hnp@rawm, after incubation with staphylococcus aureus at room temperature for 1 hour, after irradiation with 808nm laser, after 5 minutes of treatment at 50 ℃ and after dilution, plating (scale=2 cm), and B represents the results of significant reduction in bacterial load.
Fig. 7 is a schematic diagram of experimental results under 808nm laser irradiation, wherein a indicates that bacterial liquid in hnp@rawm group can reach 50 ℃ (scale=2 cm) faster than HNP group, B indicates that hnp@rawm has a "pulling" effect on bacteria in vitro experiments, and C indicates that bacterial coating results suggest that RAWM promotes local concentration of HNP on staphylococcus aureus, and has better bactericidal effect.
Fig. 8 is a graph showing the therapeutic effect, wherein a indicates that hnp@rawm+ laser group was the best in DFI mice with staphylococcus aureus infection, and wound healing was the fastest (scale = 2 mm). After the wound bacteria are coated, the bacterial colony of the HNP@RAWM+ laser group is the least (scale=2cm), and the bacterial colony quantity of the HNP@RAWM+ laser group is compared with that of the bacterial colony of the seventh day after treatment, so that the HNP@RAWM+ laser group can be found to have good antibacterial effect on the wound.
Fig. 9 is a schematic diagram of the therapeutic effect of the wound surface simulation of the mice, a represents the clinical treatment of DFI patients in the wound surface simulation of the mice, B represents that the bacterial culture result is bacillus proteus vulgaris (scale=2 mm), the drug sensitivity result is generally sensitive to antibiotics, but the therapeutic effect of antibiotics is poor, C represents that the hnp@rawm+ laser group has excellent therapeutic effect (scale=2 cm) on the simulated wound surface infection, D represents that the wound healing is rapid, and E represents that the antibacterial effect is remarkable.
Fig. 10 is a graphical representation of the results of safety studies (0.4 mg/mL, scale = 100 μm) of PBS, RAWM, HNP and hnp@rawm on the major organs of mice at therapeutic concentrations.
Detailed Description
The invention will be further described with reference to the drawings and the implementations. The specific implementation conditions are not marked in the embodiments, i.e. are understood to be performed according to conventional conditions well known in the art or suggested by the manufacturer, and the instruments involved are conventional products available for purchase through an experimental platform, if the manufacturer is not noted.
Example 1
The preparation method of the macrophage membrane-coated hair nanoparticle comprises the following specific preparation processes with reference to fig. 1:
(1) Preparation of hair nanoparticles:
2g of black hair which is not subjected to the ironing treatment by an adult is weighed, cut into pieces for standby, and each piece is about 2-3 mm. Weigh 4g NaOH powder with ddH 2 O100 mL of a 1M NaOH solution was prepared. The volume of NaOH solution was 40-60mL/g (preferably 50 mL/g) based on the mass of adult black hair, the 1M NaOH solution was placed in a glass beaker, heated to 80 ℃, the pieces were added to the solution, and the glass rod was stirred rapidly for 5 minutes. After the hair was completely dissolved, it was cooled to room temperature. Weighing 40.0g of NaCl, 1.0g of KCl and Na 2 HPO 4 -12H 2 O 14.25g、KH 2 PO 4 1.2g, add ddH 2 O4.5L is dissolved, the pH value is regulated to 7.4, the volume is fixed to 5L by a measuring cylinder, and 1 XPBS is prepared after high-temperature high-pressure sterilization. Cutting 7000kD dialysis bags into pieces, and cutting into pieces at ddH 2 O soaking was allowed to open, the head and tail were clamped, and the hair solution was added to 7000kD dialysis bags and dialyzed in 1 XPBS solution for 24 hours at room temperature at a volume ratio of hair solution to 1 XPBS of 1:50. After the dialysis was completed, the hair solution was poured out, stirred in a stirrer at a room temperature of 100rpm/min for 1.5 hours, centrifuged at 2000rpm/min for 6 minutes to remove large particle precipitates, and the supernatant was left to be centrifuged at 12000rpm/min for 10 minutes and subjected to ddH 2 And collecting and cleaning the precipitate, and repeating the steps for 2 times to obtain the hair micron particle solution. The hair micron particle solution is evaporated to dryness at the normal pressure and the temperature of 60 ℃ and then the weight is weighed, and 1mL ddH is added according to the weight of the required hair micron particle solution after being evaporated to dryness 2 After the O solution is dissolved, the hair micron particles are crushed for 1 hour in an ice-water bath by using a 520W power ultrasonic probe under the condition that the ultrasonic is started for 3 seconds and stopped for 1 second, so that the final solution is obtained, the concentration of the Hair Nanometer Particles (HNP) is 200mg/mL, and finally the hair nanometer particles are dispersed in the water solution. Considering that HNP is easy to settle, ultrasonic treatment is recommended before experiments to uniformly distribute the nano particles.
(2) Preparation of macrophage membranes:
culturing mouse macrophage cell line RAW 264.7 with RAW 264.7 cell-specific medium (Procell, wuhan, CM-0190), under the condition37 ℃,5% CO 2 The cell culture vessel of (v/v) was used for the culture. When the cells were grown to 50% density, macrophages in a 10cm dish of 2-disc culture dish were digested with pancreatin at a concentration of 2.5mg/mL, neutralized with RAW 264.7 special medium after about 1 minute, centrifuged at 800rpm/min for 5 minutes to obtain cell pellets, and the pellets were collected by centrifugation after washing with 1 XPBS. 3mL of RIPA lysate (strong) containing 1mM PMSF (Biyun, shanghai, P0013B) was prepared, added to the cell pellet, gently blown until the solution was clear, and lysed on ice for 15 minutes. RIPA lysate (strong) can be replaced by hypotonic lysate, i.e.20 mM Tris-HCl (pH=7.5), 10mM KCl and 2mM MgCl 2 1 tablet of protease inhibitor Cocktail was added per 10 mL. The solution was then broken up for 30 minutes in an ice-water bath with a 45W power ultrasonic probe provided that the ultrasound was turned on for 2 seconds and off for 3 seconds in order to lyse the cells and rupture the cell membranes. Then taking the solution after ultrasonic treatment, centrifuging at 4 ℃ for 20 minutes at 20000rpm/min, removing cell nuclei, adding 30mL of RIPA lysate (strong) containing 1mM PMSF into an overspeed centrifuge tube, centrifuging at 100000g/min at 4 ℃ for 45 minutes, removing the supernatant, obtaining transparent round precipitates on the side wall, and blowing 1mL of PBS into the uniform transparent round precipitates to obtain macrophage membrane (RAWM) solution. And (3) continuously extruding and pushing the RAWM solution for 11 times through a 400nm membrane aperture of an Avantis extruding and pushing device to obtain the RAWM in a vesicle form, freezing and storing a part of the RAWM solution in a refrigerator at the temperature of minus 80 ℃, and quantifying the remaining protein, wherein the concentration of the membrane solution is determined to be 10mg/mL.
(3) Preparation of HNP@RAWM
Adding 200 mu L of the Hair Nano Particles (HNP) obtained in the step (1) into the RAWM solution, wherein the mass ratio of the HNP solution to the RAWM solution in a vesicle form is 2:1, mixing by blowing with a pipetting gun, and carrying out ice water bath ultrasonic treatment for 20 minutes by using a 220W power ultrasonic water bath pot to obtain HNP@RAWM.
(4) Determination of Material characterization by HNP@RAWM
The aqueous solution containing HNP@RAWM is treated by ultrasonic for 10 minutes to ensure uniform distribution of nano particles, the solution with the concentration of 0.5mg/mL is prepared, 1 mu L of the solution is dripped on a copper mesh, and after the solution is dried, the solution is put into a transmission electron microscope for observation, and the solution is shown in figure 2. As can be seen from fig. 2, the shape of the HNP encapsulated by the RAWM is approximately spherical, the cell membrane is extremely thin, and the HNP can be tightly embedded in the membrane due to the shape of the membrane being circular by the extrusion of the extruder, so that the adhesion degree between the cell membrane and the material can be stronger by the nano material prepared by the method of the invention.
The aqueous solution containing hnp@rawm was sonicated for 10 minutes to ensure uniform distribution of nanoparticles, the solution configured to a concentration of 0.1mg/mL was placed in a wash cuvette, and the Zeta potential was detected with a Zetasizer nanoparticle potentiometer, as shown in fig. 3, with the rawm successfully coated on the outer nanoparticle layer of HNP.
The immunoblotting method and coomassie brilliant blue staining method are used to determine whether the protein component contained in the cell membrane is consistent with that of the macrophage. Results referring to fig. 4, the protein species and content expression were substantially consistent after macrophages, RAWM and hnp@rawm, which indicated that RAWM had been successfully encapsulated on the surface of HNP and HNP did not affect the effective membrane composition on the surface of RAWM. And, after extracting the cell membrane, the expression of cytoskeletal protein beta-actin disappears, which indicates that the effective concentration of the extracted membrane is higher, and the specific separation and purification can be obtained.
(5) Determination of in vivo and in vitro therapeutic Effect of HNP@RAWM
Since the RAWM surface high-expression integrin alpha 4 can regulate the adhesion of leukocytes and endothelial cells by controlling the homodimerization of the connecting adhesion molecule family member JAML, the adhesion of the leukocytes and the endothelial cells can be better increased, and meanwhile, more bacteria are attracted to gather, so that more HNP is adhered to the inflammation infection site. As shown in a scanning electron microscope in FIG. 5, the adhesion efficiency of pure HNP to staphylococcus aureus is low, and after being prepared by RAWM, HNP@RAWM can pull bacteria together, so that the adhesion rate of HNP on the cell surface is increased. In vitro experiments show that after HNP@RAWM and staphylococcus aureus are incubated for 1 hour at room temperature, after being irradiated by a 808nm laser, the HNP@RAWM and staphylococcus aureus are subjected to treatment at 50 ℃ for 5 minutes and then are subjected to dilution and then plating culture, as shown in figure 6, the bacterial amount is remarkably reduced, which indicates that HNP@RAWM can concentrate bacteria more and is beneficial to the local and rapid achievement of higher temperature of material concentration. The results of the invention are verified through the temperature measurement of a thermal imager (A in fig. 7), and although the treatment temperature of the invention is 50 ℃, the bacterial liquid of the HNP@RAWM group can reach 50 ℃ faster than the bacterial liquid of the HNP group. From the electron microscope observation that hnp@rawm may have a "pulling" effect on bacteria, the difference in colony count from the plating after incubating staphylococcus aureus with the material can be found that hnp@rawm group contains more bacteria than HNP group, which indicates that RAWM can adhere to bacteria, enhancing the photo-thermal killing effect of HNP on bacteria (B in fig. 7 and C in fig. 7). After incubation for 1 hour (0.4 mg/mL) with 20. Mu.L of PBS, RAWM, HNP and HNP@RAWM, respectively, by modeling diabetic ulcer mice with local staphylococcus aureus infection model, mice were observed for wound changes on days 0, 1, 4 and 7 by irradiation with 808nm laser to 50℃for 5 minutes, and bacterial liquid plating was collected for culture. From fig. 8, it can be seen that the laser group with wound healing rate is better than the non-laser group, the hnp@rawm group in the laser group has better therapeutic effect than the HNP group (healing efficiency 90% vs 80%), the group with the best therapeutic effect (a in fig. 8); bacterial colony numbers were half less in the hnp@rawm+ laser group than in the hnp+ laser group, and were minimal compared to the other groups (B in fig. 8 and C in fig. 8). Pus from DFI patients was cultured on diabetic ulcer mice to simulate human treatment (a in fig. 9), and it was found that hnp@rawm+ laser group had a significant wound healing rate and a degree of healing of about 80% (B in fig. 9). Also, the hnp@rawm+ laser group wound colonies were significantly reduced compared to hnp+ laser and pbs+ laser groups (C in fig. 9), and hnp@rawm+ laser group treatment DFI had a realistic clinical application prospect (D in fig. 9 and E in fig. 9). And no structural changes were found in the vital organs of the experimental mice, such as heart, liver, spleen, lung and kidney as shown in fig. 10, demonstrating good safety of hnp@rawm treatment of DFI.
The above-described embodiments are intended to illustrate the present invention, not to limit it, and any modifications and variations made thereto are within the spirit of the invention and the scope of the appended claims.
Claims (7)
1. The preparation method of the macrophage membrane-coated hair nano-particles is characterized in that human hair is added into a heated alkaline solution and stirred until the hair is completely dissolved, then the hair nano-particles are prepared from the human hair after the processes of dialysis, stirring, centrifugation, evaporation to dryness and ultrasound are sequentially carried out, the macrophage membrane is obtained by a squeezing method, and then the mass ratio of the macrophage membrane to the hair nano-particles is 2:1, mixing the hair nano-particles with a macrophage membrane in proportion, and coating the hair nano-particles into the macrophage membrane in an ultrasonic water bath to obtain the macrophage membrane-coated hair nano-particles;
the temperature of the heated alkaline solution is 80 ℃, the alkaline solution is 1M NaOH solution, and the stirring time is 5 minutes; dialysis conditions were 7000kD molecular weight cut-off, dialysis in 1 XPBS solution for 24 hours; stirring is carried out for 1.5 hours at room temperature in a magnetic stirrer at a rotating speed of 100 rpm/min; centrifuging at 2000rpm/min for 6 min, collecting supernatant, centrifuging at 12000rpm/min for 10 min, collecting black precipitate, and adding ddH 2 After the O solution is washed, the centrifugation is repeated for 2 times at 12000rpm/min for 10 minutes each time; the ultrasonic condition is that the hair micron particles are crushed for 1 hour in an ice-water bath by using an ultrasonic probe with 520 and W power, and the condition is that the ultrasonic is started for 3 seconds and stopped for 1 second.
2. The method for preparing macrophage membrane-coated hair nano-particles according to claim 1, wherein the ultrasonic water bath condition is 220W, and the ice water bath is performed for 20 minutes.
3. The method of claim 1, wherein the hair nanoparticle and the macrophage membrane each have a particle size of less than 100nm.
4. The method of claim 1, wherein the preparing the macrophage membrane-encapsulated hair nanoparticle comprises: culturing a mouse macrophage line RAW 264.7, and obtaining cell sediment after digestion; cell pellet was lysed on ice with RIPA lysate containing 1mM phenylmethylsulfonyl fluoride PMSF followed by shaking the solution in an ice water bath with 45W power ultrasonic probe; centrifuging the solution after ultrasonic treatment at 4 ℃, and taking and storing the supernatant; adding the obtained supernatant into RIPA lysate containing 1mM PMSF, feeding into an ultracentrifuge tube, ultracentrifugating, discarding the supernatant, retaining precipitate, and blowing with 1×PBS to homogenize the precipitate to obtain macrophage membrane solution; continuously extruding and pushing the macrophage membrane solution by an Avantis extruding and pushing device to obtain the macrophage membrane solution RAWM in a vesicle form, and quantifying protein to determine the concentration of the solution.
5. The method of claim 4, wherein the 45W power ultrasonic probe is used to shake the solution in an ice-water bath for 30 minutes, provided that the ultrasonic is started for 2 seconds and stopped for 3 seconds; centrifuging at 20000rpm/min for 20 min to remove cell nucleus; ultracentrifugation conditions were 100000g/min, centrifugation at 4℃for 45 min; the extruding aperture of the Avantis extruding device is 400nm, and the extruding times are 11 times.
6. A macrophage membrane-encapsulated hair nanoparticle prepared based on the method of any one of claims 1-5.
7. Use of hair nanoparticles coated with macrophage membrane according to claim 6 for the preparation of a medicament for the treatment of diabetic foot ulcers with infections.
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