61 results about "Bacterial outer membrane vesicles" patented technology

The invention provides a bacterial outer membrane vesicle presenting Stoppin peptide as well as a construction method and application of the bacterial outer membrane vesicle, and relates to the technical field of biological medicines. According to the invention, a fusion protein ClyA-Stoppin is firstly designed and synthesized, and the fusion protein ClyA-Stoppin is displayed on the surface of the bacterial outer membrane vesicle by using a genetic engineering technology, so that the engineered bacterial outer membrane vesicle W-Stoppin OMV for targeting presentation of Stoppin peptide is successfully constructed. The W-Stoppin OMV provided by the invention has a remarkable inhibition effect on invasion and migration of tumor cells and can be used for remarkably promoting apoptosis of the tumor cells. According to the present invention, with the Stoppin monopeptide, the problems of insufficient Stoppin cell penetrability and difficult intracellular delivery are effectively solved, compared with the Stoppin monopeptide, the Stoppin monopeptide shows the excellent anti-tumor effect, and the migration inhibition, the invasion inhibition and the apoptosis promotion effects on the tumor cells are significantly increased. The W-Stoppin OMV provided by the invention has huge application potential in the aspect of preparation of anti-tumor drugs.

A plasmid capable of automatically inserting a membrane-localized luciferase reporter gene into a chromosome of a bacterium / recipient bacterium. After the plasmid inserts a luciferase reporter gene into a chromosome of a bacterium / recipient bacterium, the plasmid can be lost. Since the plasmid can be lost, the bacterium / recipient bacterium into whose chromosome the luciferase reporter gene is inserted does not require the addition of antibiotics during subsequent use, providing convenience and reducing interference.

The invention provides a bacterial outer membrane vesicle drug carrier with a targeting effect and preparation, and relates to the technical field of biological medicines.The bacterial outer membrane vesicle protein ClyA derived from an escherichia coli W3110 strain is combined with iRGD protein capable of being combined with an integrin receptor alpha v beta 3, a ClyA-iRGD-pGEX-6P-1 recombinant plasmid for expressing ClyA-iRGD fusion protein is constructed, and the ClyA-iRGD-pGEX-6P-1 recombinant plasmid is used for preparing the bacterial outer membrane vesicle drug carrier with the targeting effect. By endogenous expression of the plasmid in W3110 escherichia coli, the C-iRGD-OMVs which has a tumor targeting effect and shows ClyA-iRGD fusion protein on the surface is prepared. The C-iRGD-OMVs shows efficient targeting binding capacity to MCF-7 breast cancer cells, overcomes the defect that iRGD single peptide is prone to aggregation and crystallization, has the potential of loading drugs, lays a foundation for the C-iRGD-OMVs serving as a targeting carrier for delivering breast cancer treatment drugs, and is expected to be further developed into a targeting treatment preparation for breast cancer.

The invention relates to the technical field of biology, in particular to a preparation method and application of a bionic nano regulator. The invention provides a bionic nano regulator. The nano regulator comprises a therapeutic drug; the therapeutic drug is prepared from Ce6 and SB525334. And extruding the bacterial outer membrane vesicles and the PLGA encapsulating the Ce6 and SB525334 medicines to obtain the bionic nano regulator. Under photodynamic therapy, the bionic nano regulator can be recognized, taken and delivered to tumor tissues by neutrophils. The bionic nano regulator can regulate and control polarization of neutrophil to an anti-tumor N1 type, promote the neutrophil to release neutrophil elastase, specifically kill tumor cells and reverse a tumor immunosuppression microenvironment. Under the combined treatment of photodynamic-immunotherapy, the biomimetic nano regulator obviously inhibits tumor growth and enhances the anti-tumor immune response of the body.

The application provides a kind of bacterial outer membrane vesicle based on acid-sensitive peptide label and its preparation method and application, it is related to the technical field of engineered bacterial outer membrane vesicle.The ClyA-pHLIP fusion protein is designed and synthesized in the application, and the pHA-W3110OMV stably expressing the ClyA-pHLIP fusion protein is successfully obtained by using genetic engineering technology.The pHA-W3110OMV effectively solves the problem of easy aggregation of pHLIP in acidic environment, has good stability and solubility, and provides conditions for the stable targeting performance of pHLIP.Meanwhile, the pHA-W3110OMV not only retains the characteristics of targeting tumor cells in acidic environment, but also realizes the characteristics of targeting tumor cells in non-acidic environment.The pHA-W3110OMV has high targeting tracing efficiency on tumor cells under different pH conditions, and can realize qualitative and quantitative detection of tumor cells in peripheral blood, and has application potential in circulating tumor cell detection and tumor primary and metastasis localization.

The present invention provides a method for preparing an antibiotic carrier based on bacterial outer membrane vesicles, characterized in that the preparation method comprises the following steps: (1) culturing bacteria in a culture medium containing antibiotics; (2) removing live bacteria from the culture medium and extracting the bacterial outer membrane vesicles, thereby obtaining an antibiotic carrier based on bacterial outer membrane vesicles; wherein the bacteria is a Salmonella mutant strain QS0074, whose deposit number is CCTCC M 2023192; and the antibiotic is acamycin. The antibiotic carrier based on bacterial outer membrane vesicles provided by the present invention has an excellent drug loading capacity for acamycin and good drug activity stability; the preparation method of the present invention is simple and easy to promote.

The invention provides an anti-tumor peptide modified bacterial outer membrane vesicle and a preparation method thereof, and relates to the technical field of engineering bacterial outer membrane vesicles. According to the invention, a recombinant plasmid capable of expressing a ClyA-A25 fusion protein in a prokaryote is designed and constructed, and the engineering bacterium outer membrane vesicle W-A25OMV modified by the anti-tumor peptide A25 is successfully prepared by using the recombinant plasmid. The W-A25OMV retains the basic structure of bacterial outer membrane vesicles, enhances the anti-tumor biological activity of A25 peptide, has good stability, shows a remarkable inhibition effect on invasion and migration of tumor cells, can effectively promote apoptosis of the tumor cells, and has development and application potential as an anti-tumor drug.

The invention discloses a bacterial outer membrane mixed vesicle carrier, the mixed vesicle is a mixed membrane structure formed by fusing two heterotype bacterial outer membrane vesicles, and the two heterotype bacteria are respectively gram-positive bacteria and gram-negative bacteria. The mixed vesicle carrier can simulate a natural internalization path of pathogenic bacteria (G < + > / G <->) invading cells, accurately locks cells which are easily invaded by bacteria, can identify corresponding homologous bacteria surfaces, efficiently enriches drugs at bacterial infection parts, and effectively improves treatment on mixed bacterial infection parts.

The invention discloses a fusion membrane packaged gold-iron core-shell nano diagnosis and treatment preparation as well as a preparation method and application thereof. The preparation takes gold-iron core-shell nanoparticles as a core, and the surface of the gold-iron core-shell nanoparticles is coated with a biomimetic membrane formed by fusion of bacterial outer membrane vesicles and tumor cell membranes. The preparation method comprises the steps of synthesis of the gold-iron nano core, surface functionalization and self-assembly coating of the fusion membrane. The preparation can simultaneously exert photothermal therapy and ferroptosis induction effects under near-infrared light irradiation, effectively initiates tumor cell immunogenicity death, and cooperatively activates dendritic cells and enhances T cell immune response by means of a pathogen related molecular mode carried by the fusion membrane and a tumor related antigen. Experiments show that the preparation can significantly inhibit tumor growth and metastasis, induce long-acting anti-tumor immune memory, and provide a multi-mode synergistic nano platform for tumor immunotherapy.

The invention provides a bacterial outer membrane vesicle based on genetic engineering modification as well as preparation and application thereof, and relates to the technical field of biological medicines. According to the invention, through a genetic engineering technology, a bacterial outer membrane protein ClyA from escherichia coli W3110 is combined with a tumor killing peptide KLAK, and a recombinant plasmid ClyA-KLAK-pGEX-6P-1 for expressing a ClyA-KLAK fusion protein is constructed; the plasmid is transformed into W3110 escherichia coli to realize endogenous expression of the fusion protein, and the engineered outer membrane vesicles C-KLAK-OMVs with anti-tumor activity are successfully prepared. On the basis that the original morphology of the bacterial outer membrane vesicle is reserved, the anti-tumor activity of KLAK is also reserved, migration and invasion of tumor cells HGC27 and MDA-MB-231 can be remarkably inhibited, and apoptosis of the tumor cells HGC27 and MDA-MB-231 is promoted; meanwhile, the medicine loading potential is realized; in addition, the C-KLAK-OMVs also improves the problem of insufficient stability of the KLAK peptide in serum, and provides a new thought and reference for targeted therapy of tumors.

The invention discloses an in-situ vaccine for tumor antigen capture driven by a nano motor as well as a construction method and application of the in-situ vaccine. The preparation method comprises the following steps: mixing prepared enzyme-immobilized dendritic silicon dioxide nanoparticles and drug-loaded bacterial outer membrane vesicles, extruding, carrying out solid-liquid separation, dispersing the obtained solid with a solvent, co-incubating the obtained suspension with pH-responsive membrane disrupting peptides and receptor molecules of targeted tumor cells, and carrying out freeze-drying to obtain the drug-loaded dendritic silicon dioxide nano-particles with the pH-responsive membrane disrupting peptides. The in-situ vaccine captured by the tumor antigen driven by the nano motor is obtained. The preparation method is green, simple and easy to operate. The in-situ vaccine can rapidly capture, enrich and release tumor-associated antigens and deliver the tumor-associated antigens to APCs, so that the reduction of curative effect caused by tumor heterogeneity and antigen degradation is avoided, the antigen presentation efficiency is remarkably improved, and the immune response is further enhanced; and the method is suitable for various tumors and has universality.

The invention discloses a nano-vesicle composition for inhibiting tumor metastasis after radiotherapy, which is characterized in that the nano-vesicle is an engineered bacterial outer membrane vesicle (OS-D), and the composition also comprises a pH responsive phospholipid modification component and a small interfering RNA (siRNA) capable of silencing CCDC25 gene expression; the siRNA is used for inhibiting formation of neutrophil Extracellular Traps (NETs) induced by radiotherapy and tumor cell migration and metastasis mediated by the NETs by blocking the interaction between the NETs and tumor cells, so that the effect of inhibiting tumor metastasis after radiotherapy is realized. The nano-vesicle composition provided by the invention can specifically block tumor metastasis mediated by neutrophil extracellular traps in a tumor microenvironment so as to enhance the effect of tumor postoperative radiotherapy and chemotherapy and effectively inhibit tumor metastasis and relapse.

The invention discloses a composite microneedle with bacterial outer membrane vesicles loaded with active ingredients as well as a preparation method and application of the composite microneedle. The composite microneedle is prepared from the bacterial outer membrane vesicles and the active ingredients loaded in the bacterial outer membrane vesicles, the bacterial outer membrane vesicles are derived from mucus eubacterium, the active ingredient is cycloastragenol, and the composite microneedle has a transdermal delivery function and delivers the active ingredient to a target tissue in a targeted manner. The method comprises the following steps: firstly, encapsulating cycloastragenol into mucus eubacterium outer membrane vesicles through a co-incubation or active drug loading technology to form a composite nano-carrier; the EL-OMVs-CAG compound prepared by the invention has good biocompatibility and blood brain barrier penetrating ability, and can target a central nervous system, regulate the activity of microglial cells, inhibit neuroinflammatory response and reduce synaptic loss and neuronal apoptosis in a hippocampal region, so that cognitive function impairment caused by operation and anesthesia is improved.

The invention relates to a preparation method and application of an anti-Parkinson hydrogel preparation, solves the problems of oxidative stress of the brain of Parkinson and dysbacteriosis of intestinal flora, and adopts the technical scheme that the anti-Parkinson hydrogel preparation is prepared by the following steps: extracting bacterial outer membrane vesicles of alcaligenes faecalis through an ultracentrifugation method; the preparation method comprises the following steps: complexing cerium ions and polyphenol substances into a metal polyphenol network, loading the cerium metal polyphenol network into bacterial outer membrane vesicles by a mechanical extrusion method, and finally mixing the substances with inulin to obtain the anti-Parkinson hydrogel preparation. The preparation conditions are mild, the process is simple, the method is stable and reliable, the production cost is low, a new thought for treating the Parkinson's disease is developed, and the traditional Chinese medicine composition is an innovation for treating the Parkinson's disease and has huge economic and social benefits.

The application provides an E. coli outer membrane vesicle targeting TLR2 receptor and a construction method thereof, and relates to the technical field of biological medicine. The application first constructs a ClyA-HLYV fusion protein, and successfully obtains a recombinant plasmid ClyA-HLYV-pGEX-6P-1 stably expressing the fusion protein through genetic engineering technology, and induces endogenous expression of the fusion protein in an E. coli W3110 strain, to prepare a targeted bacterial outer membrane vesicle (HLYV-OMVs) expressing the ClyA-HLYV fusion protein on the surface. The HLYV-OMVs prepared by the application not only retain the specific recognition ability of HLYV to the surface TLR2 receptor of breast cancer cells, but also have the potential to encapsulate drugs, realizing the dual functions of targeted recognition and drug delivery. In addition, the HLYV-OMVs effectively solve the key problem of long-acting time of HLYV single peptide in targeted application, have good stability, significantly accelerate the effect starting speed after HLYV combines with the receptor, and lay an important foundation for efficient targeted treatment of tumors.

The invention provides a bacterial outer membrane vesicle capable of efficiently targeting tumors and a preparation method of the bacterial outer membrane vesicle, and relates to the technical field of biological medicines. The target protein PDL1 binding peptide is successfully modified on the surface of the bacterial outer membrane vesicles to prepare the bacterial outer membrane vesicles PDL1-OMVs, the particle size range of the bacterial outer membrane vesicles PDL1-OMVs is 20-250 nm, and the bacterial outer membrane vesicles PDL1-OMVs have an obvious saucer-like double-layer membrane structure and accord with the structural characteristics of the bacterial outer membrane vesicles. According to the PDL1-OMVs provided by the invention, on one hand, the defect that the PD-L1 binding peptide is weak in targeting efficacy is improved, the targeting capability of the PD-L1 binding peptide is remarkably improved, on the other hand, targeting function transformation is realized on the bacterial outer membrane vesicles, and the PDL1-OMVs can realize a specific targeting effect on tumor cells, so that conditions are provided for the PDL1-OMVs serving as a carrier for targeted delivery of tumor drugs.

The invention provides an escherichia coli outer membrane vesicle (OMVs-ClyA-NRP1) with a ClyA-NRP1 fusion protein displayed on the surface as well as a preparation method and application of the escherichia coli outer membrane vesicle, and relates to the technical field of biological medicines. The OMVs-ClyA-NRP1 effectively retains the tumor targeting activity of the NRP1 protein on the basis of maintaining the typical form and structure of the outer membrane vesicles of bacteria, shows excellent targeting binding capacity to breast cancer cells MDA-MB-231, and remarkably accelerates the interaction process of the NRP1 protein and tumor cells. Meanwhile, the vesicle system also has good drug loading potential. According to the invention, the bacterial outer membrane vesicles are modified through a genetic engineering technology, so that the bacterial outer membrane vesicles have targeted binding capacity with breast cancer cells, and a new strategy is provided for targeted therapy of breast cancer.

The invention belongs to the technical field of biological medicine and nano-drug delivery, and particularly relates to a long-acting growth hormone (hGH) wrapped bacterial outer membrane vesicle and application, and the outer membrane vesicle GH-OMVs wraps a human growth hormone mutant with an amino acid sequence shown as SEQ ID NO: 1. The GH-OMVs provided by the invention can be used for preparing medicines or preparations for preventing and / or treating diseases related to growth hormone deficiency or growth hormone-related metabolic disorder, including but not limited to growth hormone deficiency, dwarf / low height, osteoporosis and the like, and has a good clinical application prospect.

The invention provides an Escherichia coli outer membrane vesicle with a tumor targeting effect and a construction method thereof, and relates to the technical field of engineering transformation of Escherichia coli outer membrane vesicles. According to the invention, the tumor vascular targeting peptide GX1 is modified on the surface of the bacterial outer membrane vesicle, so that the escherichia coli outer membrane vesicle with a tumor targeting effect is successfully obtained. The escherichia coli outer membrane vesicle not only can realize a specific targeting effect on cancer cells, but also remarkably improves the problem of insufficient targeting of the tumor blood vessel targeting peptide GX1. The Escherichia coli outer membrane vesicle provided by the invention is expected to be used as a carrier for targeted delivery of antitumor drugs for further development and research.

The application provides a kind of high-efficiency tumor-targeting bacterial outer membrane vesicle and its preparation method, it is related to biological medicine technical field.The target protein PDL1 binding peptide is successfully modified on the surface of bacterial outer membrane vesicle to prepare bacterial outer membrane vesicle PDL1-OMVs, its particle size range is between 20-250nm, with obvious tea tray like double membrane structure, meet the structural characteristics of bacterial outer membrane vesicle.The PDL1-OMVs provided by the application improves the weak targeting efficiency of PD-L1 binding peptide on the one hand, significantly improves the targeting ability of PD-L1 binding peptide, on the other hand, realizes the targeted functional modification of bacterial outer membrane vesicle, and PDL1-OMVs can realize specific targeting effect on tumor cells, which provides conditions for it as a targeted delivery tumor drug carrier.

The present invention discloses a biomimetic inorganic nanoparticle with antigen capture capability and a preparation method thereof. The biomimetic inorganic nanoparticle comprises a bacterial outer membrane vesicle, wherein the bacterial outer membrane vesicle is coated with Prussian blue-manganese dioxide inorganic nanoparticles, the vesicle wall of the bacterial outer membrane vesicle is embedded with a photosensitizer Ce6, and the outer surface of the vesicle wall of the bacterial outer membrane vesicle is modified with maleimide. After the nanomaterial is injected into the tumor, MnO2 catalyzes H2O2 to produce O2 to solve the problem of hypoxia at the tumor site. PB and Ce6 respectively play a PTT / PDT synergistic role in killing tumor cells, inducing cell immunogenic death and releasing tumor antigens. Mal captures the released antigens by forming a thioether bond. In addition, OMV contains danger signals derived from the bacterial outer membrane, stimulates dendritic cells to mature, and stimulates a strong tumor immune response. The above mechanism can synergistically and efficiently kill tumors and prevent their metastasis and recurrence, thereby achieving efficient treatment of colorectal cancer.

The invention relates to a preparation method and application of an oral vaccine based on bacterial outer membrane vesicles, which can be effectively applied to preparation of drugs for preventing or treating intestinal mucosa pathogen infection and overcome the problems of poor compliance and low mucosa immune response of traditional injection vaccines. The preparation method comprises the following steps: firstly preparing bacterial outer membrane vesicles of alcaligenes faecalis, then preparing DSPE-PEG-antigens, mixing the bacterial outer membrane vesicles and the DSPE-PEG-antigens, stirring to prepare OMV-DSPE-PEG-antigens, dissolving inulin in PBS, heating, oscillating, cooling to room temperature, adding the OMV-DSPE-PEG-antigens, stirring, and standing to obtain the finished oral vaccine. The preparation process is simple, the method is stable and reliable, operation is easy, the production cost is low, the prepared oral vaccine based on the bacterial outer membrane capsule can effectively stimulate immune response of intestinal mucosa and prevent infection of mucosa pathogens, and economic and social benefits are remarkable.

The invention belongs to the technical field of biological medicines, and particularly discloses ultrasonic responsive nanoparticles based on gene engineering bacterium outer membrane vesicle-liposome fusion as well as a preparation method and application of the ultrasonic responsive nanoparticles. The nanoparticle OLatCe6 provided by the invention can break through the bottleneck of tumor immunotherapy through a triple synergistic mechanism: (1) immune targeting enhancement: PAMPs rich in OMVs in a fusion shell can be efficiently recognized by antigen presenting cells in a tumor microenvironment, so that the tumor antigen presentation efficiency is remarkably improved; (2) intelligent immune regulation and control: a core slowly-released GM-CSF strongly recruits DCs to a tumor microenvironment and promotes maturation of the DCs, and a persistent immune response hub is established; and (3) sonodynamic-immune synergy: the sonosensitizer embedded in the lipid bilayer explodes ROS under ultrasonic irradiation, accurately induces tumor cells ICD and releases DAMPs, activates deep infiltration of cytotoxic T lymphocytes, and forms an anti-tumor immune positive feedback cycle.

The invention discloses an integrated delivery system and a preparation method and application thereof, and belongs to the technical field of biological medicine. According to the invention, positively charged dendritic macromolecules and plasmids form compound nano-particles, and the compound nano-particles are wrapped by engineered bacterial outer membrane vesicles to form an integrated delivery system. The integrated delivery system can solve the problems that matrix-rich tumors have matrix barriers, gene drugs are difficult to deliver and immune cells are difficult to infiltrate, is simple to prepare, has a series of effects of high tumor accumulation capacity, good biocompatibility and the like, realizes synchronous treatment of three different cell targets of tumor tissues, and has a wide application prospect. The pancreatic cancer immunopotentiator can be used for synergistically attacking a physical barrier, a chemotactic factor barrier and an immunosuppression barrier in a pancreatic cancer matrix, enhancing the lethality of CD8 + T cells and enhancing the immunotherapy effect, and has a good practical application value.

This invention relates to a genetically engineered bacterial outer membrane vesicle and its preparation method. By using in-cell peptides to attach exogenous proteins to the surface of OMVs via peptide bonds, a variety of desired antigens can be conveniently delivered. The reaction conditions are mild, less affected by antigen size, and unlike the SpyCatcher / SpyTag system, the in-cell peptides do not remain in the mature protein after attaching the exogenous protein to the OMV surface. This invention can serve as a universal tool for simultaneously or separately displaying different antigens on the surface of OMVs.

The invention provides a bacterial outer membrane vesicle as well as a preparation method and application thereof. Mediated cell-penetrating peptide and chlorotoxin are co-expressed on the surface of the bacterial outer membrane vesicle. The polypeptide can efficiently pass through BBB and specific targeting tumor cells in vitro and in vivo, and ferroptosis of tumor cells is induced by stimulating IFN-gamma released by CD8 + T cells in vivo, so that growth of glioblastoma is remarkably inhibited. In addition, the IFN-gamma enhances the ferroptosis of the tumor cells caused by the ferroptosis inducer RSL-3 and the erastin. The invention further provides a pharmaceutical composition, the RSL-3 is loaded to the OMV-C-C (at) RSL-3 nano delivery system formed by OMV-C-C, and the OMV-C-C and the RSL-3 show a good synergistic effect in the aspect of inhibiting the growth of glioblastoma.

The present invention belongs to the technical field of preparation of anti-tumor drugs, and more specifically, relates to a drug-loaded bacterial outer membrane vesicle that targets and intervenes in the tumor neural microenvironment and a preparation method thereof. The drug-loaded bacterial outer membrane vesicle includes a bacterial outer membrane vesicle, and a small molecule drug with a neuroinhibitory effect wrapped by the bacterial outer membrane vesicle, and the surface of the bacterial outer membrane vesicle is also modified with a nerve cell targeting molecule. The drug-loaded bacterial outer membrane vesicle provided by the present invention can effectively target nerves in the tumor microenvironment, while effectively blocking the interaction between nerves and tumors, inhibiting nerve infiltration and nerve axon growth in the tumor microenvironment, and thus inhibiting tumor growth. The preparation method of the present invention is simple and highly operable, and the prepared drug-loaded bacterial outer membrane vesicle has good biocompatibility and good clinical application prospects.

This invention belongs to the field of biomedical technology and relates to a fusion protein, gene, expression vector, genetically engineered bacteria, and their applications. The fusion protein is derived from the fusion of bacterial outer membrane vesicle protein and human PD-L1, or from the fusion of bacterial outer membrane vesicle protein, human PD-L1, and human Fc protein. Genetically engineered bacteria constructed using the fusion gene provided by this invention can release PD-L1-rich outer membrane vesicles, which can effectively penetrate the lamina propria of the mucosa and regulate inflammation inside and outside the intestine. This genetically engineered bacterium exhibits good biosafety, effectively regulating intestinal flora and metabolism, and improving intestinal barrier function; moreover, it shows good oral administration compliance, which is beneficial for clinical trials.

The invention provides a polypeptide-modified bacterial outer membrane vesicle and application thereof in preparation of a drug for promoting cell growth, and relates to the technical field of biological medicines. According to the invention, a growth promoting polypeptide VTPYGGGGVLLY with a brand new structure is designed on the basis of two micromolecular polypeptides VTPY and VLLY from sea cucumbers, and the engineering bacterial outer membrane vesicle W-VTPVLY OMV with a relatively strong growth promoting effect is prepared by combining the growth promoting polypeptide VTPYGGGGVLLY with bacterial outer membrane protein ClyA by utilizing a genetic engineering technology. The W-VTPVLY OMV provided by the invention has a remarkable promoting effect on HUVEC cell proliferation, migration and revascularization, can play a role in promoting cell proliferation within a short time, and can maintain the proliferation promoting effect for a relatively long time. The W-VTPVLY OMV provided by the invention is expected to become a new medicine for promoting wound regeneration and tissue healing, and provides a new thought and application reference for the fields of tissue engineering and medical materials.

The invention discloses a chemical crosslinking type bacterial outer membrane vesicle-PD-L1 composite nano preparation as well as a preparation method and application of the chemical crosslinking type bacterial outer membrane vesicle-PD-L1 composite nano preparation. According to the nano preparation, outer membrane vesicles derived from fecal bacillus rodent are taken as a delivery carrier, and an anti-PD-L1 antibody is stably coupled to the surfaces of the vesicles under the chemical cross-linking action of DSPE-PEG-NHS, so that the composite nano preparation MVs / alpha-PD-L1 is formed; in-vitro experiments show that the composite nano preparation can significantly inhibit the activity of breast cancer cells and induce apoptosis of the breast cancer cells; in a 4T1 in-situ breast cancer mouse model, tumor growth can be effectively inhibited, a tumor immune microenvironment can be remodeled, the biological safety is good, and a safe and effective novel delivery system is provided for targeted immunotherapy of breast cancer.