52 results about "M2 Macrophage" patented technology

Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.

The invention discloses double-target polypeptide of a tumor-associated macrophage, a nano particle, preparation and an application and relates to the technical field of bioscience and drug carriers.The double-target polypeptide is prepared by series connection of alpha helix polypeptide, a catenation sequence and M2 macrophage target peptide in a covalent bond form. The nano particle prepared bythe double-target polypeptide can perform efficient targeted transportation of drugs to the tumor-associated macrophage, so that the tumor-associated macrophage is specifically eliminated and tumor growth is inhibited; a preparation technology of the nano particle targeting to the tumor-associated macrophage is simple; large-scale production is facilitated; most raw materials for preparing the nano particle are used clinically or used in clinical experiments; and a detection result shows that no toxic or side effects are caused on physiologic and biochemical indexes of a mouse.

The invention provides application of miR-1246 and / or TERF2IP in diagnosis and treatment of glioma. The fact that that microRNA-1246 (miR-1246) is the most abundant microRNA expressed in glioma-derived exosomes (GDEs) and is significantly up-regulated in anoxic glioma-derived exosomes (H-GDEs) is disclosed for the first time. In addition, the miR-1246 is also enriched with exosomes isolated from cerebrospinal fluid (CSF) of a patient with preoperative glioblastoma (GBM), and the exosomes miR-1246 in cerebrospinal fluid of the patient with GBM after tumor resection are significantly reduced. The MicroRNA-1246 is shown to have the strongest capability to induce polarization of M2 macrophages. In addition, studies find that H-GDEs-induced M2 macrophage polarization is mediated by the miR-1246 / TERF2IP / STAT3 and miR-1246 / TERF2IP / NF-kappa B pathways.

The present invention features methods of directly targeting specific cell surface receptors on the M2 macrophage for antibody or nanoparticle directed therapy.

The invention relates to lactobacillus casei with immunoregulation, anti-inflammatory and anti-cervical cancer effects. The lactobacillus casei strain is named as LH23, the preservation number is CGMCC No.16656, and the strain can be used for regulating immunity, regulating M1 / M2 macrophage balance, increasing the number of Treg cells, improving the symptoms of mouse colitis, shortening the colonlength and apoptosis of intestinal epithelial cells, inhibiting excessive secretion of proinflammatory factors (TNF-alpha, IL-1beta and IL-6) and recovering the concentration of short-chain fatty acid(SCFAs) in the intestinal tract, can resist cervical cancer, inhibit proliferation of cervical cancer HeLa cells and acetylation modification of histone, cause apoptosis of the HeLa cells and inhibitexpression of human papilloma virus HPVE6 and E7 proteins. The strain is used for preparing fermented food for inhibiting inflammatory bowel diseases and cervical cancer, and has a very wide application prospect.

The invention discloses a macrophage-derived exosome preparation for resisting inflammation and promoting tissue regeneration and a preparation method and application of the macrophage-derived exosome preparation. The macrophage-derived exosome preparation comprises an M2 type macrophage source exosome. The macrophage-derived exosome preparation can be used for preparing medicines, health-care products or nutritional supplements for treating inflammatory diseases, tissue repair and degenerative diseases. The M2 macrophage exosome preparation is simple to prepare, wide in material source and convenient to store, compared with cell therapy, the exosome is small in side effect and not prone to causing immune response, can regulate inflammation balance, promote wound healing and slow down the progression of degenerative diseases after being applied, can be applied in various forms and has good clinical application value.

The invention relates to a lipid nano-scale ultrasound contrast agent for targeting tumor-associated macrophages as well as a preparation method and application thereof. The lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages disclosed by the invention takes lipids as a shell membrane material, and wraps low-molecular-weight hyaluronic acids and gaseous fluorocarbon in the shell membrane; and the lipids consist of dipalmitoyl-phosphatidylcholine (DPPC), distearoyl-phosphatidylethanolamine (DSPE) and distearyl phosphatidylethanolamine-polyethylene glycol-folic acids (DSPE-PEG-FOL). The lipid nano-scale ultrasound contrast agent has a particle size of 255-497 nm, and is capable of passing through vascular wall space of tumor tissue so as to achieve tumortreatment effects with passive targeting and high efficiency; PEG chain is utilized so as to have coupled folic acids located outside the lipids shell membrane and the low-molecular-weight hyaluronicacids wrapped in the contrast agent, so that it is ensured that the lipid nano-scale ultrasound contrast agent for the targeting tumor-associated macrophages can actively target the tumor-associatedmacrophages by a folic acid-folic acid receptor way; and the low-molecular-weight hyaluronic acids act on the tumor-associated macrophages, so that the tumor-associated macrophages can be transformedfrom type-M2 macrophages into type-M1 macrophages.

Described herein are chimeric receptors. Chimeric receptors comprise a cytoplasmic domain; a transmembrane domain; and an extracellular domain. In embodiments, the cytoplasmic domain comprises a cytoplasmic portion of a receptor that when activated polarizes a macrophage. In further embodiments, a wild-type protein comprising the cytoplasmic portion does not comprise the extracellular domain of the chimeric receptor. In embodiments, the binding of a ligand to the extracellular domain of the chimeric receptor activates the intracellular portion of the chimeric receptor. Activation of the intracellular portion of the chimeric receptor may polarize the macrophage into an M1 or M2 macrophage.

The invention provides a polypeptide aggregate used for regulating subtype transformation of macrophages and a preparation method and application thereof. The polypeptide aggregate comprises a targeting unit, a morphology transformation driving unit and an aggregation driving unit which are connected in sequence by amide bonds; the targeting unit includes a polypeptide sequence targeting a type M2macrophage. The polypeptide aggregate adopts a segmented design, and the targeting unit targeting the type M2 macrophage, the morphology transformation driving unit and the aggregation driving unit are integrated into a polypeptide molecule, then efficient assembly of the polypeptide aggregate in vitro and precise targeting and site-selective reassembly of the polypeptide aggregate in vivo are realized, transformation of the type M2 macrophage to a type M1 macrophage is realized, and meanwhile, the specificity, precision and efficiency of subtype transformation are guaranteed. Meanwhile, thepolypeptide aggregate has good biocompatibility, and is regarded as a molecule for realizing subtype transformation of the macrophages, and has higher biological safety.

The invention discloses a preparation method and application of a nano material with a synovial immunoregulation function, and belongs to the technical field of biologication.The key point of the technical scheme is that the preparation method comprises the following steps that S1, constructing shRNA-LeptinR: specifically, inserting a synthesized shRNA-LeptinR fragment into a plasmid vector to obtain a recombinant plasmid vector, then, transforming the recombinant plasmid vector into escherichia coli, and extracting the shRNA-LeptinR plasmid; S2, preparing a macrophage membrane; S3, preparing gene-loaded nanoparticle M2H@RPK: preparing the nanoparticle M2H@RPK by adopting an electrostatic adsorption method; and wrapping the nanoparticle H@RPK with the M2 macrophage membrane extracted in the step S2, and repeatedly passing through a polycarbonate membrane by using a micro extruder to obtain the nanoparticle M2H@RPK. The invention is mainly used for inhibiting synovial immune response and relieving inflammatory cascade reaction in the OA process.

The invention discloses a preparation method and application of a nano material with a synovitis inhibition function, and belongs to the technical field of biology. According to the key point of the technical scheme, the preparation method comprises the following steps that S1, shRNA-LeptinR is constructed, specifically, a synthesized shRNA-LeptinR fragment is inserted into a plasmid vector to obtain a recombinant plasmid vector, then, the recombinant plasmid vector is transformed into escherichia coli, and the shRNA-LeptinR plasmid is obtained through extraction; S2, a macrophage membrane is prepared; and S3, gene-loaded nanoparticles M2H@RPK is prepared, specifically, the nanoparticles M2H@RPK is prepared by adopting an electrostatic adsorption method, the nanoparticles H@RPK is wrapped with the M2 macrophage membrane extracted in the step S2, and a polycarbonate membrane repeatedly passes through by using a micro extruder to obtain the nanoparticles M2H@RPK. The preparation method is mainly used for relieving the inflammatory cascade reaction in the OA process, and the nano-system targets the cartilage matrix and can effectively relieve joint injury and inhibit the severity of overall arthritis.

The invention specifically relates to a gene and chemical small molecule co-delivery system and an application in tumor treatment. In the drug co-delivery system, small interference RNA targeting indoleamine 2,3-dioxygenase-1, and gemcitabine are loaded in a 2-methylimidazole zinc metal-organic framework nano-cage in a combined manner for the first time to relieve immunosuppression related to regulatory T cells and myeloid-derived suppressor cells; then a mineralization substance which can produce oxygen is mineralized on the nano-carrier surface to reduce immunosuppression of M2 macrophage; and after a therapeutic ICB antibody is modified on the mineralized shell surface, a multifunctional nano-regulator is constructed. The multifunctional nano-regulator integrates multiple efficacies, stimulates a "hot" tumor microenvironment, and greatly enhances ICB treatment of "cold" malignant tumors.

The invention belongs to the field of biological medicine, and relates to a macrophage exosome membrane coated bionic nanoparticle as well as a preparation method and application thereof, and the macrophage exosome membrane coated bionic nanoparticle is formed by an exosome membrane coated nanoparticle PLGA (at) Dnmt3aossmartsilencer; the exosome membrane is separated from M2 macrophages from bone marrow; and the nano-particle PLGA (at) Dnmt3aossmartsilencer is formed by co-emulsification of a polylactic acid-glycolic acid copolymer PLGA and Dnmt3aossmartsilencer. Compared with the prior art, the application has the advantages that the EM-PLGA-(at) Dnmt3aossmartsilencer is used for remarkably inhibiting polarization of M2 macrophages in the allergic asthma (AA), the bionic medicine is effectively accumulated in the lung and promotes gene silencing, and meanwhile, the infiltration degree of inflammatory cells to the airway is reduced. Therefore, the PLGA NP based on the M2 macrophage exosome membrane is beneficial to delivery of the therapeutic Dnmt3aossmartsilencer to the airway, and the therapeutic Dnmt3aossmartsilencer is guided to be more effective in treatment in an AA mouse model.

The invention relates to the technical field of new complications of drug, in particular to application of guaiol in preparing drug for inhibiting tumor related M2 macrophage, and discloses the drug for inhibiting the tumor related M2 macrophage. Experiments find that guaiol can modify M2 macrophage phenotype and promote conversion of the M2 macrophage into macrophage which is not activated by inducing, has obvious inhibiting effect on expression of macrophage surface marker, expression of cell factors secreted by the macrophage, expression of mRNA of the M2 macrophage and expression of M2 macrophage protein and achieves the objective of inhibiting tumor growth, invasion and metastasis by inhibiting the M2 macrophage so as to realize tumor treatment. Guaiol serving as a low-toxicity high-efficiency antitumor substance has great medicinal prospect, and a new idea is provided for tumor treatment.

The present invention features methods of directly targeting specific cell surface receptors on the M2 macrophage for antibody or nanoparticle directed therapy.

The invention discloses application of LINC01503 serving as therapeutic target to preparation of medicines for treatment of pediatric asthma. According to comparison between LINC01503 and a normal control, expression of LINC01503 in asthma patients is increased remarkably; LINC01503 in M1 macrophage is evidently down-regulated while LINC01503 in M2 macrophage is evidently up-regulated. According to siRNA knock-down experiments, LINC01503 promotes activation of M1 macrophage and realizes expression up-regulation of M1 marker genes such as IL-6, TNF-alpha and CXCL10; LINC01503 inhibits activation of M2 macrophage and realizes expression down-regulation of M2 marker genes such as CD206 and CD209. By Western blot, the fact that LINC01503 has influences on macrophage activation mainly through promotion of EPK phosphorylation, so that pediatric asthma can be effectively treated by inhibition of LINC01503 and downstream signal routing thereof.

A method of treating a disease or disorder that can benefit from increasing an M2 / M1 macrophage ratio in a subject in need thereof is provided. The method comprising: (a) culturing basophils in the presence of IL33 and / or GM-SCF; and (b) administering to the subject a therapeutically effective amount of the basophils following the culturing, thereby treating the disease or disorder that can benefit from increasing an M2 / M1 macrophage ratio in the subject.

The invention relates to the technical field of chemical medicines, in particular to a supermolecule precursor, a supermolecule assembly and a method for regulating and controlling macrophage polarization. The supermolecule precursor comprises polycation modified by cyclodextrin, and adamantine-polyethylene glycol-active polypeptide loaded to the polycation modified by cyclodextrin, wherein an active peptide raw material for forming the adamantine-polyethylene glycol-active polypeptide can be the polypeptide capable of regulating and controlling the macrophage polarization. The supermolecule precursor can effectively regulate and control polarization from macrophage to M2 macrophage, meanwhile, the supermolecule precursor can load RNA, and therefore, the supermolecule assembly can furtherregulate and control the macrophage polarization so as to accelerate the macrophage to be converted into the M2 macrophage.

The invention provides an in vitro method for inducing macrophage polarization to an M2 phenotype useful for tissue repair. The method described in the present invention comprises the in vitro exposure of macrophages to repeated series of hypoxia-reoxygenation. Activated M2 macrophages obtained by this method overexpress molecules important for tissue remodeling and amelioration of inflammation, such as NGAL and anti-inflammatory cytokines (IL-10). Thus, M2 macrophages obtained by this method are useful as cell therapy for tissue regeneration. The invention also provides pharmaceutical compositions and kits comprising the M2 macrophages obtained by the described method. The invention further refers to a device for inducing hypoxia and re-oxygenation conditions on isolated macrophages according to the described method.

The invention belongs to the technical field of gynecological disease diagnosis and treatment, and discloses application of an M2 macrophage in blood vessel barrier protection, and prevention, inhibition and treatment of ovarian cancer ascites. The M2 macrophage is researched to reconstruct a molecular mechanism of a damaged blood vessel barrier, a discovery result shows that the M2 macrophage inhibits the expression of a VCAM-1 (vascular cell adhesion molecule-1) in endothelial cells, and therefore, an ROS (reactive oxygen species) level and the phosphorylation of VE-cadherin can be lowered to protect the blood vessel barrier. In addition, an ovarian cancer animal model is constructed and is combined with a clinical sample to discover that the macrophage in the ovarian cancer regulates the blood vessel barrier through a VLA-4 (very late antigen-4) / VCAM-1 approach to affect the development of malignant ascites, so that a new approach is confirmed, and a new strategy is provided for treating the ovarian cancer ascites.

CD206-positive M2 macrophage-targeting exosomes and methods of use thereof are provided. One embodiment provides a CD206-positive M2 macrophage-targeting exosome expressing a CD206 binding peptide and an Fc portion of IgG2b. In some embodiments, the CD206 binding peptide is encoded by a nucleic acid sequence having 95%, 99%, or 100% sequence identity to SEQ ID NO:2 and the IgG2b is encoded by a sequence having 95%, 99%, or 100% sequence identity to SEQ ID NO:6.

A method of treating a central nervous system disease, the method including administering an agent including a therapeutically effective amount of vitamin B12 to a patient with a central nervous system disease to treat the central nervous system disease. This disclosure also relates to a method of promoting M2 macrophage / microglia induction, inhibiting M1 macrophage / microglia induction, and / or reducing the ratio of M1 macrophage / microglia to M2 macrophage / microglia in a patient in need thereof, the method including administering an agent including a therapeutically effective amount of vitamin B12 to the patient to promote M2 macrophage / microglia induction, inhibit M1 macrophage / microglia induction, and / or reduce the ratio of M1 macrophage / microglia to M2 macrophage / microglia. This disclosure also relates to a pharmaceutical product including vitamin B12.

The invention provides a preparation method of an anti-tumor nanoparticle drug. According to the method, etidronic acid is taken as a core, etidronic acid and carboxymethyl chitosan modified with two groups of imidazole and mannose are prepared into the nanoparticle drug by means of ionic gelation, treatment effect on resistance to malignant tumor is realized by targeting to a lot of M2 macrophages present at the tumor lesion part and enabling the macrophages to apoptosis so as to intervene the microenvironment for existence of tumor, targeting performance of nano in malignant tumor treatment is realized, drug entrapment efficiency of nanoparticles is avoided, and steps of anti-tumor nanoparticle drug preparation are simplified. Since anti-tumor effect of the drug is achieved without chemotherapeutic drugs, the anti-tumor nanoparticle drug cannot cause toxic and side effects similar to chemotherapeutic drugs while treating malignant tumor.

The invention discloses a macrophage-based living cell drug-carrying system, a preparation method and application thereof. The macrophage-based live cell drug delivery system comprises macrophages, anchored chemotherapeutic drugs and anchored cytolytic groups. The preparation method includes the following steps: taking mouse bone marrow cells, culturing them in vitro, adding recombinant mouse macrophage colony stimulating factor and mouse breast cancer 4T1 cell culture supernatant or lipopolysaccharide LPS into the culture medium, and continuing to culture, Induce macrophage polarization to obtain regulatory M1 or M2 macrophages; co-incubate anchored chemotherapeutic drugs and anchored cytolytic groups in macrophage culture medium to prepare macrophage-based Live cell drug delivery system. The macrophage-based living cell drug-loading system prepared above can actively target the lung metastasis site of breast cancer, and effectively inhibit the lung metastasis of breast cancer.

Compositions and methods for domain-specific targeting of CD206 are presented in which selected agents bind to the carbohydrate recognition domain 4 (CRD4) and carbohydrate recognition domain 5 (CRD5) of CD206. In certain aspects of the inventive subject matter, binding is specific, leads to a conformational change of CD206, and will induce phagocytosis in tumor associated macrophages and / or M2 macrophage cell death.

A preparation of silver nanoparticles has been found to be effective in improving functional and behavioral recovery from traumatic spinal cord injury. The silver nanoparticles are provided in a non-flowable gel vehicle, from which they are release at high efficiency, that is applied locally at the site of the spinal cord injury. Silver nanoparticle formulations described herein were found to modify the M1 / M2 macrophage phenotype ratio and provides a synergistic effect in the combination with arginase to promote healing processes at the treated injury site, reducing postinjury inflammation.

The invention relates to the technical field of biomedicine, in particular to the application of polypeptides in regulating macrophage transformation in vitro. The polypeptide provided by the present invention composed of the amino acid sequence shown in SEQ ID No.1 is derived from leeches. The inventors have found through research that the polypeptide can efficiently promote the transformation of M1 macrophages to M2 macrophages in vitro, and the transformation The effect is remarkable and stable, and it is suitable for in vitro batch transformation. At the same time, the polypeptide composed of the amino acid sequence shown in the sequence SEQ ID No.1 can exist stably in in vitro preparations, and is suitable for preparing related regulation products for long-term transportation, storage and large batches use. The polypeptide composed of the amino acid sequence shown in the sequence SEQ ID No. 1 is used in drug efficacy evaluation or scientific research using the transformation of M1 type macrophages into M2 type macrophages as a detection index.

The present invention relates to the field of immunology and to methods for inducing an M1 / Th1 dominated immune response in an M2 macrophage dominated and / or Th2 / Treg dominated human patient or animal. These methods are useful for developing therapies for treating or preventing M2 macrophage mediated and / or Th2 / Treg mediated disease states.