30 results about "Macrophage targeting" patented technology

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 belongs to the field of pharmacy, and discloses a synthesis method of a macrophage targeting carrier system and a preparation method of a gene delivery system. The macrophage targeting carrier system is characterized in that a macrophage targeting carrier is mannosylation protamine; electropositive mannosylation protamine loads electronegative nucleic acid to form a positively charged nano particle; and protamine modified by carubinose is prepared from formyl methyl mannopyranoside and protamine sulfate through a reductive amination reaction. Compared with non-viral gene carrier protamine, mannosylation protamine has a nuclear localization function and a macrophage targeting property, and can improve the gene transfection mediation efficiency of protamine in macrophage. The preparation method is simple, and mature in technology, and has good application prospects.

The invention relates to a nano particle carrier having tumor and tumor-associated macrophage targeting multiple functions, which can be used for tumor therapy and in vivo imaging and positioning. The carrier is a liposome nano particle mediated by a tumor focus induction-activated cell-penetrating peptide, can be specifically enriched on the tumor focus through a circulating system after being subjected to intravenous injection, and simultaneously has the functions of molecule imaging and carrying multiple biomacromolecules and medicines. Concretely, by using a TAT cell-penetrating peptide of closed active center amino acid of a Legumain specificity-identified enzyme digestion substrate to connect PEG-modified liposome nano particles, after the circulating system reaches the tumor focus position, Legumain expressed by tumor and tumor-associated macrophage can separate the enzyme digestion substrate from the TAT active center, thereby realizing the enrichment on the tumor focus. The nano particle can pack various biomacromolecules or medicines, and has the functions of killing tumor, in vivo tumor tracing and performing early prevention on tumor.

The invention relates to a macrophage tumor targeting therapy system combining a photothermal therapy effect and photo-thermally responsive biotherapeutic factor release and preparation and application thereof. The unique spatial and temporal selectivity of the macrophage tumor targeting therapy system can direct at a variety of solid malignant tumors, combines tumor photo-thermal therapy with biological therapy to achieve the local targeted comprehensive treatment of the tumors and reduce the toxic and side effects of traditional treatment caused by an off-target effect. The macrophage targeting tumor system can effectively inhibit the tumor growth of mice and prolong the survival time of the tumor-bearing mice, is an excellent tumor-targeting biological preparation and has great clinicalconversion application prospects.

The invention provides a macrophage targeting carrier system. Specifically, the invention provides a macrophage targeting nano-particle carrier system, components of the nano-particle carrier system, a preparation method of the nano-particle carrier system and an application of the nano-particle carrier system to the aspects of medicines and nucleic acid delivery. The main body material of the nano-particles provided by the invention has biodegradability, biocompatibility and delayed slow release property, and can be injected locally or wholly. Moreover, the synthesis method is simple, convenient and efficient, the surfaces of the prepared nano-particles contain high-density targeting elements, and the medicines and genes can be efficiently delivered to macrophages in a targeted mode. The nano-particles rich in targeting elements and the developing agents can be specifically enriched in macrophages and are used for diagnosis and treatment of diseases.

The invention designs and synthesizes a graft polymer of mannan and phosphatidylethanolamine (PE) and the polymer is used as ligand and applied to the surface modification of nanocarrier. The invention belongs to the chemical technical field and is characterized in that the hydrophilic site of glycosyl, the hydrophobic site of lipid radical and the negative mannan ligand are prepared by chemosynthetic method with simple synthesis method and high yield; the products are applicable to the surface modification of nanocarrier of gene with positive ions of various carrier materials; because the mannan targets the mannose receptor on the surface of macrophage, the modified nanocarrier can react on the murine macrophage with low cytotoxicity, thus realizing the targeting transfection of macrophage of nanocarrier. The targeted graft polymer used as ligand is applicable to the surface modification of nanocarrier of gene with positive ions.

The invention belongs to the technical field of biology, and relates to novel application of mesenchymal stem cell source exosomes, in particular to building of lncRNA MALAT1 modified fat source mesenchymal stem cells and preparation of the exosome of the mesenchymal stem cells, and application of the exosome to preparation of a hepatic disease treatment biological agent and a liver macrophage targeted biological agent. According to the thought, MALAT1 modified AMSCs are built, and the exosome is prepared; through experiments such as ELISA, WB and streaming in the cell level, the regulation and control advantages of the AMSC-MALAT1-Exo on the macrophage functional phenotype are defined; through in vivo experiments, the curative effect on hepatic diseases and the action advantages on the regulation and control of the liver macrophage functional phenotype of the MALAT1 modified AMSC source exosome are defined. The liver macrophage targeted biological agent or medicine with the improved curative effect is further prepared.

The invention discloses a nanoparticle for macrophage targeting drug delivery and a preparation method thereof. First, curcumin-carrying nanoparticles are prepared by oil-in-water solvent evaporation method, the surface of the curcumin-carrying nanoparticles is modified with chondroitin sulfate, the particle size of the nanoparticles is 281.5 + / -3.51nm, and the narrow particle size distribution and the higher drug loading amount can be rezlized. The chondroitin sulfate is introduced into the surface of the nanoparticles, and by scanning electron microscope observation, the nanoparticles are round or oval, and the size is more uniform. Compared with the nanoparticles with the surface modified with carboxymethyl cellulose, the chondroitin-sulfate-modified nanoparticles significantly increase the phagocytosis efficiency and anti-inflammatory effect, and the therapeutic efficiency of colitis can be effectively enhanced.

The invention belongs to the technical field of molecular biology and in particular relates to a tumor blood vessel and M1 type macrophage targeting peptide and application thereof. Aiming at the problem that a small molecular targeting peptide for preparing a medicine for diagnosing or treating tumors is lacked, the invention provides the tumor blood vessel and M1 type macrophage targeting peptide TCP-2 and a carrier thereof. The small molecular targeting peptide has an amino acid sequence shown as SEQ ID NO: 1, can be used for specifically targeting tumor blood vessels and M1 type macrophages and can be used for preparing the targeting medicine for diagnosing or treating the tumors; especially, the mall molecular targeting peptide is used for treating digestive tract tumors and providesa new choice for targeting therapy of the tumors.

The invention discloses a macrophage-targeted mTORC1 activator for controlling NASH progression. The invention provides the application of a substance capable of reducing the activity of mTORC1 in macrophages in the preparation of a product capable of promoting progression of non-alcoholic steatohepatitis to hepatic fibrosis. By studying the effect of mTORC1 in macrophages on the non-alcoholic steatohepatitis, it is found that the progression of non-alcoholic steatohepatitis can be accelerated by inhibiting the activity of mTORC1 in macrophages. The invention is of great reference significancefor the research on the pathogenesis of non-alcoholic steatohepatitis and for the selection of future treatment strategies.

The invention discloses a vesicle nano-drug loaded with a chloroquine compound as well as a preparation method and application of the vesicle nano-drug. The vesicle nano-drug loaded with the chloroquine compound is prepared by taking a polymer and a chloroquine compound as raw materials, wherein the polymer comprises a hydrophilic chain segment and a hydrophobic chain segment; a side chain of the hydrophobic chain segment is dithiolane containing a disulfide bond. According to the vesicle nano-drug loaded with the chloroquine compound disclosed by the invention, a safe and efficient macrophage-targeted nano-drug is researched and developed for treating rheumatoid arthritis; polymer vesicles are designed for efficiently loading, carrying out targeted delivery and controlling to release drug hydroxychloroquine or chloroquine, so that the enrichment of the drug in cytoplasm is improved; M1M is re-polarized to M2M, so that secretion of proinflammatory cytokines is reduced and secretion of anti-inflammatory cytokines is increased; and the drug can be used for inhibiting DC activation and also can be used for removing ROS and enriching in inflammatory joints. In-vitro and in-vivo experiment results prove that the vesicle nano-drug loaded with the chloroquine compound can be used for carrying out targeted treatment on the rheumatoid arthritis.

The invention relates to a preparation method and application of a macrophage tracer fluorescent probe. According to the probe, one of amino acids essential for human bodies, namely lysine, is adoptedfor chemical crosslinking with carboxymethyl dextran to form uniform and stable dextran crosslinking nanoparticles, imaging small molecules such as indocyanine green are connected through covalent bonds on the nanoparticles, and thus nanoparticles with both a macrophage targeting capability and an imaging capability are constructed. The probe prepared by the invention has good macrophage targeting performance and high biosecurity.

The invention discloses miRNA for preventing and / or treating acute pancreatitis, and pharmaceutical application of the MiRNA, and belongs to the technical field of biological medicines. The invention provides application of a miR-133a agonist in preparation of a medicine for inhibiting the acute pancreatitis, and makes clear that the miR-133a agonist is miRNA of which the nucleotide sequence is shown as SEQ ID NO: 1. Through simulation of a clinically related acute pancreatitis model, the miR-133a agonist is proved to be capable of remarkably improving occurrence and development of the above AP model, and can be used for clinically preventing / treating the AP. Meanwhile, the invention also proves through an in-vitro acinus cell AP model that the protection effect of the miR-133a agonist for the acute pancreatitis is that macrophages carry out targeted "removal" on the damaged acinus cells to realize the functions of alleviating the AP inflammatory response and reducing AP severity. The invention provides a new drug source for prevention, diagnosis, detection, protection, treatment and research of pancreatitis diseases, can be easily popularized and applied clinically, and can generate a huge clinical application prospect and social benefit in a relatively short time.

A bispecific cytotoxic lymphocyte or macrophage-redirecting autoantibody comprising a cytotoxic lymphocyte or macrophage targeting domain and an autoantibody. Methods for producing bispecific cytotoxic lymphocyte or macrophage-redirecting autoantibody comprising a cytotoxic lymphocyte or macrophage targeting domain and an autoantibody. Methods for treating a subject in need thereof comprising administering to the subject an isolated bispecific cytotoxic lymphocyte or macrophage-redirecting autoantibody.

The invention belongs to the field of pharmacy, and discloses a synthesis method of a macrophage targeting carrier system and a preparation method of a gene delivery system. The macrophage targeting carrier system is characterized in that a macrophage targeting carrier is mannosylation protamine; electropositive mannosylation protamine loads electronegative nucleic acid to form a positively charged nano particle; and protamine modified by carubinose is prepared from formyl methyl mannopyranoside and protamine sulfate through a reductive amination reaction. Compared with non-viral gene carrier protamine, mannosylation protamine has a nuclear localization function and a macrophage targeting property, and can improve the gene transfection mediation efficiency of protamine in macrophage. The preparation method is simple, and mature in technology, and has good application prospects.

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.

The invention belongs to the technical field of molecular biology, and specifically relates to a tumor blood vessel and M1 type macrophage targeting peptide and its application. Aiming at the problem of lack of small molecule targeting peptides used for preparing drugs for diagnosis or treatment of tumors, the present invention provides a tumor vessel and M1 type macrophage targeting peptide TCP‑2 and its carrier. The small-molecule targeting peptide has the amino acid sequence shown in Seq ID NO: 1, can specifically target tumor blood vessels and M1 macrophages, and can be used to prepare targeted drugs for diagnosis or treatment of tumors, especially for use in For the treatment of gastrointestinal tumors, it provides a new option for targeted therapy of tumors.

The invention discloses tuberculosis vaccine and a preparation technology thereof. The tuberculosis vaccine is prepared from recombinant lentivirus expression plasmid pLenti-spHIL47 / pLenti-spHII1 andlentivirus packaging the recombinant lentivirus expression plasmid. The tuberculosis vaccine can obviously improve mycobacterium tuberculosis antigen presenting capacity of macrophage, can enhance a vaccine function for stimulating a body to generate antigen specificity immune response, can effectively activate the macrophage infected by mycobacterium tuberculosis, improves autophagy level of themacrophage and improves mycobacterium tuberculosis killing and cleaning functions of the macrophage. The tuberculosis vaccine disclosed by the invention can effectively promote the body to clean infected mycobacterium tuberculosis in the body; when the tuberculosis vaccine disclosed by the invention and tuberculosis chemotherapy drugs are combined and used, a tuberculosis treating period is remarkably shortened; when the tuberculosis vaccine disclosed by the invention and tuberculosis chemotherapy drugs are combined and used, tuberculosis relapsing can be remarkably delayed after the tuberculosis is treated; compared with other lentiviral vector vaccines, the tuberculosis vaccine disclosed by the invention has good macrophage targeting and use safety.

The present invention relates to a visceral adipose tissue macrophage-targeted non-viral gene / carrier complex for preventing and treating obesity-induced type II diabetes. More specifically, the gene / carrier complex according to the present invention delivers a therapeutic gene in a stable manner in a case of being injected into the body with the visceral adipose tissue macrophages being targeted, and thus exhibits an excellent inhibitory effect against TACE, which allows the gene / carrier complex to be applied for prevention or treatment of obesity-induced type II diabetes.

The invention discloses an immunoregulation microsphere preparation targeting tumor-associated macrophages (TAMs) as well as a preparation method and application of the immunoregulation microsphere preparation. The microsphere preparation is a double-targeting preparation binding macrophage targeting peptide and B cell lymphoma 6 (Bcl6) factor inhibiting peptide; and the microsphere preparation isprepared as follows: the Bcl6 factor inhibiting peptide is supported on a liposome to obtain a Bcl6 factor inhibiting peptide-liposome solution; and then, the Bcl6 factor inhibiting peptide-liposomesolution is bound with the macrophage targeting peptide. The macrophage targeting peptide and an intracellular signal molecule inhibitor are bound for the first time and supported on nano microspheresto prepare the immune preparation directionally transferred to a tumor microenvironment. Besides, the preparation is found to be able to significantly reduce the proportion and number of macrophagesin lung cancer tumor and reverse stem cell-like phenotypes of the macrophages for the first time, and the preparation can significantly inhibit the size and weight of the lung cancer tumor and has a remarkable antitumor function.

The invention belongs to the field of biological medicine, and particularly relates to CKIP-1 RNAi compound of macrophage targeted and a preparation method and application thereof. The CKIP-1 RNAi compound is formed by fusion peptides and CKIP-1 RNAi which are connected and combined through an electrostatic interaction; the fusion peptides are composed of V6 peptides and T9 peptides; and the nucleotide sequence of the CKIP-1 RNAi is as shown in SEQ ID NO.4. The fusion peptides are compounded, purified and then are connected and combined with the CKIP-1 RNAi to obtain the CKIP-1 RNAi compound.The CKIP-1 RNAi compound specifically targets CD11b receptors on the surfaces of macrophages and meanwhile efficiently transfects the macrophages, and expression of the CKIP-1 and activation of the macrophages are inhibited, so that inflammatory response of cerebral hemorrhage mediated by the macrophages is inhibited, and the CKIP-1 RNAi compound can be used for preparing anti-inflammatory drugs for treating the cerebral hemorrhage mediated by the macrophages, and good development application prospects are achieved in the cerebral hemorrhage field.

The invention discloses a genetic engineering cell membrane bionic nano-microsphere with pancreatic cancer microenvironment targeting and a preparation method of the genetic engineering cell membrane bionic nano-microsphere. The tumor-associated macrophage targeting peptide is expressed on the surface of pancreatic cancer cells KPC in a lentivirus transfection mode, and a pancreatic cancer cell line overexpressed by the macrophage targeting peptide M2pep is constructed; a pancreatic cancer first-line chemotherapy drug gemcitabine is loaded in a polylactic acid-glycollic acid polymer by a multiple emulsion method, and polylactic acid-glycollic acid nanoparticles are formed by self-assembly; the cell membrane vesicles of a pancreatic cancer cell line are extracted by using a gradient centrifugation method, and the polylactic acid-glycollic acid nano-microspheres are entrapped to obtain the pancreatic cancer microenvironment enhanced targeting gene engineering cell membrane bionic nano-microspheres. The cell membrane bionic nano-microspheres can be enriched in pancreatic cancer tissues in a large amount, non-specific accumulation of other tissues in a body is reduced, a specific targeting effect on the pancreatic cancer tissues is achieved, and the cell membrane bionic nano-microspheres have the advantage of accurately delivering a chemotherapeutic drug gemcitabine to the pancreatic cancer tissues in a large amount.

The invention relates to a preparation method and application of a fluorescent probe for macrophage tracing. The probe chemically cross-links carboxymethyl dextran with lysine, one of the essential amino acids for human body, to form uniform and stable dextran. Glycan cross-linked nanoparticles, on which small imaging molecules such as indocyanine green were covalently linked, constructed nanoparticles with both macrophage targeting and imaging capabilities. The probe prepared by the invention has better macrophage targeting ability and higher biological safety.

The invention relates to a nano particle carrier having tumor and tumor-associated macrophage targeting multiple functions, which can be used for tumor therapy and in vivo imaging and positioning. The carrier is a liposome nano particle mediated by a tumor focus induction-activated cell-penetrating peptide, can be specifically enriched on the tumor focus through a circulating system after being subjected to intravenous injection, and simultaneously has the functions of molecule imaging and carrying multiple biomacromolecules and medicines. Concretely, by using a TAT cell-penetrating peptide of closed active center amino acid of a Legumain specificity-identified enzyme digestion substrate to connect PEG-modified liposome nano particles, after the circulating system reaches the tumor focus position, Legumain expressed by tumor and tumor-associated macrophage can separate the enzyme digestion substrate from the TAT active center, thereby realizing the enrichment on the tumor focus. The nano particle can pack various biomacromolecules or medicines, and has the functions of killing tumor, in vivo tumor tracing and performing early prevention on tumor.

The invention relates to a macrophage tumor targeting therapy system combined with photothermal therapy effect and photothermal responsive biotherapeutic factor release, as well as its preparation and application. The unique spatiotemporal selectivity of this macrophage tumor targeting therapy system can target a variety of solid malignant tumors, combined with tumor photothermal therapy and biological therapy, to achieve local targeted comprehensive treatment of tumors, and reduce the traditional treatment due to off-target effects. toxic side effect. The macrophage-targeting tumor system can effectively inhibit the growth of tumors in mice and prolong the survival of tumor-bearing mice. It is an excellent tumor-targeting biological agent and has great prospects for clinical transformation.

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 designs and synthesizes a graft polymer of mannan and phosphatidylethanolamine (PE) and the polymer is used as ligand and applied to the surface modification of nanocarrier. The invention belongs to the chemical technical field and is characterized in that the hydrophilic site of glycosyl, the hydrophobic site of lipid radical and the negative mannan ligand are prepared by chemosynthetic method with simple synthesis method and high yield; the products are applicable to the surface modification of nanocarrier of gene with positive ions of various carrier materials; because the mannan targets the mannose receptor on the surface of macrophage, the modified nanocarrier can react on the murine macrophage with low cytotoxicity, thus realizing the targeting transfection of macrophage of nanocarrier. The targeted graft polymer used as ligand is applicable to the surface modification of nanocarrier of gene with positive ions.

Methods and formulations to target and activate B-1a lymphocytes and / or macrophages are described. The methods and formulations can be delivered to the respiratory tract to target B-1a lymphocytes and / or macrophages in the pleural cavity. Conditions with inflammatory or autoimmune components can be treated. B-1a lymphocytes and / or macrophages can be targeted and activated using fibrils or fibril-forming peptides.

The invention belongs to the field of biotechnology, and relates to the new application of exosomes derived from mesenchymal stem cells, in particular to the construction of adipose-derived mesenchymal stem cells modified by lncRNA MALAT1 and the preparation of exosomes, and its application in the preparation of biological preparations for liver disease treatment and Application of liver macrophage targeting biologics. The idea of ​​the present invention is to construct MALAT1-modified AMSC, prepare its exosomes, and clarify the regulatory advantages of AMSC-MALAT1-Exo on the functional phenotype of macrophages at the cellular level through ELISA, WB, flow cytometry and other experiments, and through in vivo The experiment clarified the curative effect of MALAT1-modified AMSC-derived exosomes on liver diseases and its role in regulating the functional phenotype of liver macrophages. And further prepare liver macrophage targeting biological preparations or drugs with improved curative effect.

The present invention relates to a visceral adipose tissue macrophage-targeted non-viral gene / carrier complex for preventing and treating obesity-induced type II diabetes. More specifically, the gene / carrier complex according to the present invention delivers a therapeutic gene in a stable manner in a case of being injected into the body with the visceral adipose tissue macrophages being targeted, and thus exhibits an excellent inhibitory effect against TACE, which allows the gene / carrier complex to be applied for prevention or treatment of obesity-induced type II diabetes.