389 results about "Endocytosis" patented technology

The invention belongs to the technical field of biological medicine, and discloses an engineering bionic exosome with an anti-aging effect and a preparation method and application thereof, and the preparation method comprises the following steps: (S1) preparing a bionic cell membrane modified targeting ligand: adding collagen, mitochondrial targeting polypeptide, a condensing agent and 4-dimethylaminopyridine into an organic solvent, and stirring to obtain the bionic cell membrane modified targeting ligand; activating under a protective atmosphere, and then adding lysine into the system to react, so as to obtain a bionic cell membrane modified targeting ligand; and (S2) embedding the bionic cell membrane modified targeting ligand into the engineered exosome bionic membrane, and entrapping an active substance to form the engineered bionic exosome. The exosome provided by the invention has better skin permeability, mitochondrial targeting effect and cell endocytosis effect, has better protection effect on mitochondria, and can realize efficient delivery of active substances.

Provided are a bispecific antibody, a drug conjugate thereof, and a use thereof. The bispecific antibody comprises an EGFR binding domain and an HER3 binding domain. The provided bispecific antibody and the drug conjugate thereof have excellent endocytosis effects, proliferation inhibition activity and tumor growth inhibition activity, as well as good in vivo safety.

The invention provides an antibody specifically combined with CDH6 (cadherin 6) and application thereof, and particularly discloses mouse and humanized antibodies combined with CDH6 as well as a preparation method and application thereof, and the mouse and humanized antibodies have better affinity with CDH6 protein and better endocytosis activity, so that the mouse and humanized antibodies can be applied to preparation of medicines for treating tumors and the like.

The present invention the invention concerns bifunctional compounds of Formula (I) A-T-L1-AG, Formula (II) A-L1-Con(L2-AG)n or Formula (III) Ak´-Th-L3 ii-AGj' wherein A is a protein that binds to the hinge region of galactose deficient IgA1 antibodies or a protein that binds to autoantibodies of galactose deficient IgA antibodies and AG is an asiaglycoprotein receptor binding moiety (ASGPR binding moiety). L1, Con and L2 are part of a linker between A and AG. The A has the ability to bind to antibodies that are a cause of IgA nephropathy and the asiaglycoprotein receptor binding moiety binds to hepatic cells thereby initiating endocytosis and removal of the antibodies that are a cause of IgA nephropathy from the blood stream.

The invention relates to an antibody endocytosis efficiency detection method based on fluorescence resonance energy transfer, and belongs to the technical field of antibody endocytosis detection. The method comprises the following steps: coupling succinimide ester with an amino-containing compound to obtain a quenching agent, incubating an antibody to be detected and a target cell together, adding a fluorescence-labeled secondary antibody to carry out endocytosis reaction, removing an extracellular fluorescence signal by using the quenching agent after the reaction is finished, and detecting an intracellular fluorescence signal to obtain the endocytosis percentage of the antibody to be detected. The detection method provided by the invention is based on a fluorescence resonance energy transfer principle, an intracellular signal direct detection method in the prior art is optimized, and an extracellular fluorescence signal is removed, so that a detection system has higher sensitivity. The quenching agent provided by the invention can also be combined with an acid eluent in the prior art to further reduce an extracellular signal background value and improve the sensitivity of a detection system, can be applied to high-throughput detection of a to-be-detected antibody, is high in sensitivity and low in detection cost, and has a good application prospect.

The invention relates to a bifunctional compound and application thereof in targeted degradation of protein, the compound comprises a target protein binding compound and a cell-penetrating peptide which are connected, and the target protein binding compound is a compound capable of binding with cell membrane protein or extracellular protein or a derivative thereof; the target protein binding compound and the cell-penetrating peptide are connected through a linker or directly connected. According to the invention, it is found for the first time that specific extracellular proteins or cell membrane proteins can enter cells in an endocytosis manner and are degraded through lysosomes by using cell-penetrating peptides and small molecule conjugates. The method disclosed by the invention has the characteristic of delivering bioactive macromolecules through endosome wrapping without depending on a single receptor, and the effect of degrading the target protein by using the cells can be realized as long as specific binding micromolecules of the protein to be degraded can be found and coupled with the cell-penetrating peptide; a widely applicable strategy is provided for degradation of extracellular proteins and cell membrane proteins.

The present invention provides an antibody or fragment thereof having binding specificity for human solute carrier 34A2 (SLC34A2) protein. These antibodies are capable of binding to SLC34A2 with high affinity, and can mediate antibody dependent cytotoxicity (ADCC) and effectively induce endocytosis. Methods and uses for treating cancer are also provided.

Provided siRNA for inhibiting XDH gene expression and a modifier and use thereof. The siRNA comprises a sense strand and an antisense strand. The sense strand and / or the antisense strand have a length in the range of 19-25 nucleotides, and the antisense strand is reversely complementary to a segment on a target gene; and the sense strand has a nucleotide sequence as shown in SEQ ID NO: 1-14, and the antisense strand has a nucleotide sequence as shown in SEQ ID NO: 18-31. siRNA molecules and modified siRNA molecules have high stability and / or high inhibitory activity. Ligand-conjugated siRNA molecules have good liver targeting performance and the capability to promote cell endocytosis while maintaining high inhibitory activity and stability, can reduce the impact on other tissues or organs and reduce the amount of siRNA molecules used, and can achieve the purposes of reducing toxicity and reducing costs.

The invention provides a targeting vector and a method for targeting a host cell, the vector comprises a first molecule combined with an endocytosis receptor of a target cell and a second molecule for promoting release of a substance carried by the targeting vector into cytoplasm, when the targeting vector is a virus vector, the first molecule is not a part of a virus envelope protein, and the second molecule is not a part of a virus envelope protein. The second molecules promote endosome escape or lysosome escape of the targeting carrier. According to the present invention, the first molecule is designed according to the endocytosis receptor of the to-be-targeted cell so as to target different types of cells, and after the vector is subjected to reasonable mutation, the infection of the cells not requiring the targeting can be avoided, and the accuracy of the vector can be improved.

The invention relates to the technical field of antibodies, in particular to a pH-sensitive humanized anti-transferrin receptor 1 antibody. The invention designs a pH-sensitive human anti-transferrin receptor 1 antibody or an antigen binding fragment thereof, the antibody has good binding activity to TfR1 under a neutral pH condition, the binding activity is obviously reduced or lost under a low pH condition, and the antibody can more efficiently penetrate through a blood-brain barrier to be delivered into the brain through a TfR1-mediated endocytosis transport effect by utilizing the pH-sensitive characteristic, so that the human anti-transferrin receptor 1 antibody or the antigen binding fragment thereof can be applied to the brain. The drug delivery system can be used as a delivery carrier of drugs for treating central nervous system diseases, and has a wide application prospect.

An anti-CDH17 antibody or an antigen-binding fragment thereof and the use thereof. The antibody can specifically bind to one or more extracellular domains in extracellular domains 1-7 of CDH17, has an ADCC activity, and can mediate cell endocytosis, thereby providing a new possibility for the treatment and / or prevention of cancers.

The invention provides a tumor vaccine based on AKK bacteria and a preparation method and application thereof.Specifically, antigen peptide is subjected to lysine, on one hand, the free positive charge content of the antigen peptide is increased, the antigen peptide is endowed with the cell penetrating capacity, the two combined cell entering modes of direct cell penetrating and endocytosis are achieved, the cell entering number and rate of the antigen peptide are successfully increased, and the cell entering efficiency of the antigen peptide is improved; on the other hand, the modified peptide fragment and a bacterial adjuvant carrier are combined through simple stirring, and preparation and application of the tumor vaccine are successfully achieved. Therefore, the invention provides a simple, effective and universal tumor vaccine construction means, and provides a new thought for development and application of the cell-penetrating peptide.

The invention relates to the technical field of biological genetic engineering, in particular to construction of recombinant lactobacillus plantarum of an African swine fever virus antigen, and the method comprises the following steps: constructing a lactobacillus plantarum shuttle vector containing different ASFV antigen genes; and referring to a genome sequence of a Chinese isolate CADCHN09 of ASFV disclosed in GenBank. The method has the advantages that an inducer is not needed, antigen protein is efficiently expressed, the dendritic cell (DC) binding peptide for enhancing immune cell uptake and processing is subjected to fusion expression, the oral immunization mode is simple, mucosal immunity is stimulated, and ASFV infection is effectively prevented and controlled; probiotics, namely lactobacillus plantarum, which naturally exist in animal intestinal tracts and can be colonized and copied in digestive tracts for a long time are used as a carrier; key epitopes of proteins such as nucleocapsid protein p72, outer envelope protein CD2v, inner envelope protein p54, p22, pE199L and pE248R, which play an important role in adsorption, internalization, endocytosis and membrane fusion of ASFV, are preferably fused with dendritic cell binding peptide and then are displayed on the surface of lactobacillus plantarum.

The present invention relates to antibodies or antibody fragments that bind to human and non-human primate transferrin receptors. The antibodies described herein can be used as agents to deliver pharmaceutical compounds into or through cells during receptor-mediated endocytosis and / or transendocytosis processes. As transferrin receptors are also present in the blood brain barrier endothelial cells, one aspect of the invention provides means and methods to increase delivery of pharmaceutical compounds to the central nervous system.

The invention discloses a nano degradation agent for targeted degradation of PI3Kalpha protein as well as a preparation method and application of the nano degradation agent. The nano degradation agent comprises a polyamidoamine dendritic polymer G3-NH2, a PI3Kalpha protein targeted receptor and an HSC70 protein targeted receptor, wherein the PI3Kalpha protein targeted receptor and the HSC70 protein targeted receptor are coupled to the surface of the polyamidoamine dendritic polymer G3-NH2. The prepared nano degradation agent enters cells in an endocytosis mode, specifically targets corresponding treatment targets after entering the cells, and then efficiently degrades PI3Kalpha protein through a molecular chaperone-mediated autophagy pathway of lysosome, so that the PI3Kalpha protein can be effectively degraded. The nano degradation agent provided by the invention can be applied to intervention of related diseases caused by PI3Kalpha protein abnormality.

The invention relates to the technical field of medical gel, in particular to gynecological vaginal mucosa repairing gel and a preparation method thereof. Comprising the following raw materials: carbomer, glycerol, sodium hyaluronate, vitamin E, potassium sorbate, a modified nano polylactic acid-glycolic acid copolymer, modified nano collagen, albumin, tea tree essential oil, aloe, astragalus membranaceus, dandelion, stigma croci and ginseng. The modified nano polylactic acid-glycolic acid copolymer, the modified nano collagen and the albumin play a role through a synergistic effect, and the modified nano polylactic acid-glycolic acid is used as a skeleton structure for cell growth and is firmly attached to the active pharmaceutical ingredient-albumin compound; the polyacrylic acid chain on the surface controls the drug release rate by sensing the change of the pH value, the albumin initiates endocytosis through specific binding, and the albumin and the modified nano collagen jointly improve the anti-inflammatory performance, promote cell proliferation and differentiation and promote repair and regeneration of vaginal mucosa tissues.

The invention provides universally acceptable “off-the-shelf” hypoimmunogenic pluripotent cells and differentiated cardiac, endothelial, neuronal, islet, or retinal pigment cells thereof. Such hypoimmune cells are used to treat patients in need thereof. The cells lack major immune antigens that trigger immune responses and are engineered to avoid phagocytic endocytosis.

The invention provides a response liposome for treating traumatic brain injury by targeting a blood-brain barrier loaded drug and a preparation method of the response liposome, and belongs to the field of traumatic brain injury treatment.The response liposome is prepared by preparing TfR-T12 target peptide firstly, then preparing nano-particles with hydrophobic molecular drugs wrapped inside, and finally preparing the TfR-T12 target peptide with the hydrophobic molecular drugs wrapped inside. And finally, preparing the response liposome for treating traumatic brain injury by the targeted blood-brain barrier loaded medicine. According to the application, the TfR-T12 target peptide which is highly expressed in cerebral cortex microvessels and can help a nano-drug to pass through a blood brain barrier through endocytosis is prepared as a target spot, meanwhile, the liposome is subjected to polypeptide modification, and the self-assembly driving force of the nano-particles is improved through process control; the outer surface of the response lipidosome is a target peptide, and the response lipidosome is internally coated with a nano-drug; the liposome can repair the blood brain barrier after injury, improve the blood flow of the brain, improve the drainage of the colloidal lymphatic system, improve the motor and cognitive functions of mice after injury, and reduce the dosage of drugs and various possible side effects caused by the drug dosage.

The invention discloses RVG29 peptide modified tripterine transfersome nasal in-situ gel and a preparation method and application thereof.The in-situ gel is mainly prepared from tripterine, soybean phospholipid, cholesterol, mPEG2000-DSPE, mPEG2000-DSPE-RVG29, sodium deoxycholate and DGG, the RVG29 peptide modified tripterine transfersome nasal in-situ gel can increase the solubility of indissolvable drugs, and the RVG29 peptide modified tripterine transfersome nasal in-situ gel has the advantages that the solubility of the indissolvable drugs is improved; and the RVG29 peptide which can be specifically recognized with a dopaminergic neuron high-expression acetylcholine receptor is modified on the surface of a carrier, so that efficient active targeting endocytosis can be effectively realized, and the RVG29 peptide can be used for treating the Parkinson's disease.

The present invention relates to the field of genetic engineering, and specifically relates to a vector and a method for transfecting non-activated T cells in vitro. Disclosed in the present invention are a vector and a method of using the vector to come into contact with non-activated T cells and transfect the non-activated T cells. The surface of the vector comprises one or more antibodies or antigen-binding fragments thereof and / or ligands or receptor binding fragments thereof that specifically bind to endocytic receptors of non-activated T cells; and the vector can carry a nucleic acid encoding a CAR, enters the non-activated T cells by means of endocytosis initiated by the specific binding of the endocytic receptors of the non-activated T cells, and then effectively transfects the non-activated T cells. Therefore, the technical problem whereby it is difficult to effectively transfect non-activated T cells in the process of preparing CAR-T cells in vitro is effectively solved, thereby reducing the cost of preparing CAR-T cells and shortening the preparation period.

The invention belongs to the field of traditional Chinese medicines, and particularly relates to an inhalation type pharmaceutical composition for treating inflammatory respiratory diseases and a preparation method thereof. The inhalation type pharmaceutical composition comprises an active component and a nano-liposome, and mannose is modified on the surface of the nano-liposome; the active ingredients comprise bulbus fritillariae cirrhosae total alkaloids and platycodin D; the nano-liposome is prepared from the following raw materials: phospholipid, cholesterol and cholesterol-polyethylene glycol 1000-mannose ester. The liposome can be specifically recognized by a mannose receptor highly expressed on the surface of alveolar macrophage through a surface-modified mannose ligand, so that the receptor-mediated endocytosis is started, and the wrapped bulbus fritillariae cirrhosae total alkaloids and platycodin D are efficiently introduced into cells. The inhaled pharmaceutical composition of the present invention collectively pushes macrophages from a pro-inflammatory M1 phenotype to a repairable M2 phenotype. Therefore, the overall curative effect of the combination of the two components is far better than that of the independent use of any component.

The invention discloses an adriamycin-tetravalent platinum drug-norcantharidin three-drug combined nano-drug as well as a preparation method and application thereof, and belongs to the technical field of medical materials. A tetravalent platinum drug modified by demethylated cantharidin and adriamycin are used as raw materials, a novel nano-drug is constructed through Cu < 2 + > coordination, and then the nano-drug combining adriamycin, the tetravalent platinum drug and demethylated cantharidin is prepared by polymerizing polydopamine with a mild photo-thermal effect. The polymer has the capacity of controllably releasing drugs under acidity and reduction, can realize photo-thermal conversion under laser irradiation to generate a mild photo-thermal effect, has a better tumor cell killing effect, has the capacity of consuming glutathione and generating hydroxyl radicals, can enter cancer cells in an endocytosis mode and release DOX, and can be used for killing tumor cells. And a new thought is provided for multi-drug combination and chemotherapy-chemokinetics therapy-photothermal therapy multi-mode combined therapy.

The invention discloses a positive charge fluorescent nanoprobe targeting BCR-ABL fusion protein and application of the positive charge fluorescent nanoprobe in leukemia single cell drug resistance detection, and relates to the field of biological medicine. According to the invention, the surface of the nanoprobe is subjected to specific modification of a polyethylene glycol hydrophilic polymer chain-bridged targeting molecule, so that the functionalized fluorescent nanoprobe with leukemia subcellular oncogenic fusion protein targeting property is successfully constructed. The probe realizes efficient and accurate targeting of the BCR-ABL fusion protein by regulating a subcellular transport pathway, completes diagnosis and quantitative analysis of drug resistance of the leukemia single-cell BCR-ABL fusion protein by utilizing an endocytosis-transport-exocytosis process of cells, can more comprehensively reveal heterogeneity and drug resistance conditions of BCR-ABL positive cells, and has a good application prospect. And a new technical means is provided for accurate diagnosis and treatment of chronic myelogenous leukemia.

The invention belongs to the technical field of biological medicine, discloses a novel venom polypeptide composite dendrimer as well as a preparation method and application thereof, and particularly discloses scorpion venom polypeptide, and the amino acid sequence of the scorpion venom polypeptide is FLGGSLSSIF. According to the invention, a novel scorpion venom polypeptide (marked as C9) is separated and identified, and a novel polypeptide-polyamidoamine dendritic compound G5C9 (i.e., nanoparticles) with a glioblastoma (GBM) targeting effect is constructed. Compared with the polypeptide C9, the cell uptake efficiency of the G5C9 is obviously improved. G5C9 can enter cells through endocytosis and target lysosome to destroy functions of the lysosome and mTORC1, so that nuclear translocation of TFEB is promoted, and autophagic death of the cells is induced. Therefore, the G5C9 provides a novel mode for targeting the anti-GBM in vitro and in vivo.

The invention discloses a nucleic acid tetrahedron nanostructure as well as a preparation method and application thereof. The nucleic acid tetrahedron nanostructure is composed of circRNA for coding an antigen, an ISD chain and two specific single-stranded DNA sequences, is simple and easy to prepare, can enter cells through cell membrane microfossa mediated endocytosis without the help of a transfection reagent, and is positioned to lysosome. The nanostructure is split to release circRNA coding antigen protein, and the circRNA coding antigen protein is delivered to APC and ISD chains in drainage lymph nodes (dLN) to activate cGAS-STING pathways, so that antigen presentation and immune activation are synergistically enhanced, T cells are efficiently and continuously activated, and the effect of tumor immunotherapy is achieved.

The invention discloses a method for detecting the assembly change of an ASGPR (asialoglycoprotein receptor) on the surface of a hepatocyte, which comprises the following steps: carrying out specific labeling on the ASGPR on the surface of the hepatocyte through an antibody, and carrying out fluorescence imaging on the ASGPR on the surface of a cell membrane, the purpose of detecting ASGPR assembly change on the liver cell membrane is achieved by statistically analyzing the number of ASGPR protein positioning points on the surface of the cell membrane and aggregation parameters. According to the method, the distribution and aggregation condition of the ASGPR on the cell surface is measured through the nanoscale resolution, the change of the ASGPR in the cell membrane assembly relation is detected, damage to sample cells is small, the time cost of the experimental process is small, protein positioning is accurate, and as the ASGPR is an endocytosis receptor specifically existing on the surface of hepatocellular carcinoma cells, the detection result is accurate, and the detection accuracy is high. Efficient treatment can be achieved through a drug delivery system formed by targeting ASGPR, ASGPR can be better known by observing the assembly difference of ASGPR on the surface of a cell membrane from the nanoscale, and the method has wide application prospects in the field of medical detection and diagnosis.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to N-methylation modified cyclopeptide and application thereof. On the basis of a GluA2-3Y polypeptide sequence, chemical modification and transformation of amido bond N-methylation and head-tail cyclization are carried out, the N-methylation modified cyclopeptide with stable metabolism and good permeability is obtained, and the endocytosis of a GluA2AMPA receptor is blocked to protect nerve cells, so that the GluA2AMPA receptor can be effectively inhibited, and the GluA2AMPA receptor can be effectively inhibited. The invention also provides application of the cyclic peptide in preparation of drugs for treating cerebral arterial thrombosis.

Provided is a polypeptide which contains a polypeptide having at least 80%, 85%, 90%, 95%, or 99% identity to amino acid sequence MTYRPGYNPFG (SEQ ID NO: 41) or amino acid sequence AKGYYRPYGVPV (SEQ ID NO: 22), or a polypeptide having one or more amino acid substitutions, deletions and / or additions relative to the amino acid sequence as shown in SEQ ID NO: 41 or 22. The provided polypeptide can interfere with the binding of a Brag2 synaptic protein to the C terminus of an AMPA receptor, thereby inhibiting NMDA-mediated excessive endocytosis of an AMPA receptor and neuronal apoptosis, and playing a role in protecting neuronal cell activity. Therefore, the polypeptide has application prospects and potential development values as a drug for treating nervous system diseases such as strokes, depression, Alzheimer's disease and drug addiction.

The invention discloses an alkyl ether ester ionizable lipid compound and application thereof. The alkyl ether ionizable lipid compound is composed of a head group R1, a linker L and a tail group R2 in sequence. According to the alkyl ether ionizable lipid disclosed by the invention, two tertiary amine centers are connected by adopting a cyclic carbon chain structure, so that the delivery effect is obviously higher than that of ionizable lipid linearly connected with the two tertiary amine centers, and by adding an ether bond-containing tail structure in the alkyl ether ionizable lipid, the cell endocytosis and the cell endosome escape effect of LNP are improved; therefore, more mRNA is delivered into a living body and translated and expressed into corresponding proteins. Therefore, compared with the ionizable lipid in the prior art, the alkyl ether ionizable lipid disclosed by the invention has a better delivery effect.

An antibody against CEACAM5 and CEACAM6 or antigen-binding fragment thereof, and the use thereof. The antibody is an antibody against CEACAM5 and CEACAM6, which antibody has a good performance, and can specifically bind to both targets CEACAM5 and CEACAM6 with a high affinity, thereby expanding antibody indications. The antibody against CEACAM5 and CEACAM6 has a binding specificity, hardly binds to normal cells, and only binds to overexpressed tumor cells, thereby reducing adverse effects caused by non-specific binding. The antibody also has a good endocytosis activity, and can be used for coupling a cytotoxic drug to form an antibody-drug conjugate for anti-tumor therapy.