249 results about "Endocytosis" patented technology

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 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 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 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 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 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 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.

The invention relates to the technical field of biology, in particular to an anti-LIV-1 antibody or an antigen binding fragment thereof, an antibody drug conjugate and application thereof. Specifically, the LIV-1 antibody obtained by the invention has higher affinity and good endocytosis rate; the antibody drug conjugate containing the antibody has a remarkable cell killing effect and has a very strong tumor growth inhibition effect. The invention also relates to application of the antibody or the antigen binding fragment thereof and the antibody drug conjugate in preparation of drugs for treating cancers, and the antibody or the antigen binding fragment thereof and the antibody drug conjugate play an important role in treatment of human tumors.

The application provides a multifunctional nano particle for targeting abdominal aortic aneurysm and a preparation method and application thereof, and belongs to the field of nanobiomedicine, wherein polyphenol oxidation self-polymer nanoparticles are used as carriers, doxycycline is loaded, and a targeting ligand cRGD is modified on the surface of the nano carrier; the neovasculature in the media and adventitia of AAA sites helps accumulation of the nanoparticles in the abdominal aortic aneurysm, and the integrin αν3 beta receptor highly expressed on the surface of the diseased cell membrane can recognize the cRGD with high affinity, and then mediate the targeted endocytosis of the nanoparticles; after intravenous injection, the nanoparticles can be effectively enriched in the lesion site and achieve long-term retention, and can release DC in response to the high ROS level in the tumor microenvironment; the drug is rapidly released to take effect, and the non-specific toxic side effects are reduced; the free radical scavenging capacity of the nanoparticles can be synergized with the DC activity to treat AAA through multiple mechanisms such as anti-inflammatory, antioxidant, macrophage repolarization promotion, anti-apoptosis and calcification inhibition, and MMPs inhibition.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell.

Therapeutic compounds for red blood cell-mediated delivery of an active pharmaceutical ingredient to a target cell are described. The therapeutic compounds are configured to bind CD47 on the surface of a red blood cell and to be subsequently transferred to CD47 on the surface of the target cell, the therapeutic compound ultimately being internalized by the target cell via endocytosis. The target cell may be a cancer cell, a virus-infected cell, or a fibrotic cell.

The invention discloses a magnetic-aptamer targeting tumor tissue nano-drug delivery system as well as a preparation method and application thereof, and belongs to the field of medicines. The system comprises a mesoporous ferroferric oxide magnetic core, a polyethyleneimine (PEI) layer coated outside the mesoporous ferroferric oxide magnetic core and an aptamer adsorbed outside the PEI layer, and an autophagy activator can be selectively loaded in the mesoporous core. The preparation method comprises the following steps: sequentially carrying out drug loading, PEI coating and aptamer modification on the mesoporous Fe3O4 nanoparticles. According to the invention, efficient enrichment and endocytosis of tumor tissues are realized through dual effects of magnetic targeting and active targeting of the aptamer; lysosome escape is promoted by using the proton sponge effect of PEI; finally, by virtue of the synergistic effect of iron ions released by degradation of the Fe3O4 nanoparticles and endogenous iron ions released by ferritin autophagy induced by an autophagy activator, ferroptosis of tumor cells is induced through enhanced Fenton-like reaction, so that high-efficiency and low-toxicity targeted therapy is realized.

The invention provides a targeted degradable protein and application thereof, and belongs to the technical field of biological medicine. The amino acid sequence of the targeted degradation protein is SEQ ID NO.1. When the targeted degradation protein is used for treating breast cancer, target protein degradation can be directly mediated, so that the effect of the target protein is weakened fundamentally, the targeted degradation protein only needs to be combined with the target protein with very strong affinity, specific epitopes do not need to be combined, the design difficulty is low, and the number of adaptive targets is large. Therefore, the targeted degradation protein provided by the invention takes the membrane molecule with high expression of tumor specificity as the effect protein, so that the dual effects of tumor targeting and mediated endocytosis are realized.

The invention relates to the technical field of cytobiology and biomedicine detection, and discloses a time sequence fluorescence tracing system based on a coupling detection lipid probe. Comprising an imaging detection module which is used for adding FM lipophilic styrene fluorescent dye in a culture environment, forming a membrane probe to observe the morphological change of a membrane and detect the formation of vesicles, and completing the complete time sequence tracing of the cell endocytosis process by adopting a content dyeing method; the deep learning module is used for carrying out deep learning on the obtained time sequence image, establishing a living cell imaging screening and image analysis system, and identifying protein molecules related to the target external vesicles; carrying out image description on the generation, transportation and fusion processes of the vesicles generated by the proteins in different stages before fusion of the outer vesicles and the cell membranes and after fusion and shearing; and the knock-down operation module is used for exploring the generation mode of the vesicle contents in the early endosome in combination with knockout and knock-down operations of the specific drug compound.

The invention discloses an auxiliary protein composition, iron oxide nanoparticles, a preparation method and application, the composition comprises an SC protein with an amino acid sequence as shown in SEQ ID NO: 1 and an ST protein with an amino acid sequence as shown in SEQ ID NO: 2, and the composition can be used for modifying the iron oxide nanoparticles. The auxiliary protein composition can effectively promote endocytosis of the iron oxide nanoparticles, and assists the iron oxide nanoparticles to realize lysosome escape; moreover, the iron oxide nanoparticles modified by the auxiliary protein composition are good in biocompatibility and long in retention and storage time in cells, can be used for long-time labeling of the cells, and have wide clinical transformation and application prospects as a cell tracer agent.

The application provides a toxicity-enhanced neurotoxin recombinant protein and application thereof, and belongs to the technical field of biological medicine. The recombinant protein comprises a botulinum toxin type A receptor binding domain and at least one GM1 binding peptide inserted into the botulinum toxin type A receptor binding domain, and the recombinin protein can recognize and bind to ganglioside GM1. The short peptide sequence capable of binding to ganglioside GM1 is introduced into the botulinum toxin type A receptor binding domain to obtain the recombinant protein, the binding capacity of the recombinant protein to ganglioside GM1 is enhanced, the target recognition and binding capacity of the recombinant protein to the nerve cell membrane are improved, the overall affinity and endocytosis efficiency of the recombinant protein to the nerve cell are improved, and the neurotoxicity of the botulinum toxin is enhanced. The application not only improves the binding efficiency of BoNT / A in the in-vitro nerve cell model, but also shows a higher toxicity level in the functional verification, and shows a good clinical conversion prospect.

The present application relates to a kind of drug composition containing STING agonist and WIP1 inhibitor and its liposome and application.The composition can be co-encapsulated in liposome with STING agonist and WIP1 inhibitor, form stable drug delivery system.The liposome can promote efficient endocytosis of cell, and release two active ingredients in cytoplasm synchronously, block the negative feedback mechanism of STING signal path by WIP1 inhibitor, enhance and prolong the activation level of STING path, to synergistically inhibit tumor growth.Based on the mechanism, the drug composition of the present application can be used for preparing the drug for treating diseases related to STING path (such as tumor).

The application discloses a LYTAG-Gem compound for enhancing the anti-tumor effect of gemcitabine and application thereof, relates to the technical field of biological medicine, and particularly relates to a gemcitabine (Gem) targeted delivery system based on a lysosome targeting chimera (LYTAC) and application thereof in enhancing the anti-tumor process. 2+ The system is assembled from heavy chain ferritin, Ni 2+ , NTA-PEG5000-DBCO and a targeting ligand TPP-1-N3 in a specific mass percentage, can efficiently load Gem and form a nano compound with a particle size of about 59-79 nm, the system targets tumor cells through heavy chain ferritin, and realizes site-specific release of Gem in cells by means of an endocytosis-lysosome pathway mediated by the LYTAC structure, in-vivo pharmacodynamic experiments show that the LYTAC-Gem compound can significantly inhibit the tumor growth of a KPC pancreatic cancer mouse model, molecular mechanism research further reveals that the LYTAC-Gem compound can down-regulate the expression of PD-L1 protein in tumor tissues, and it is indicated that the LYTAC-Gem compound has the potential to activate an anti-tumor immune response, and the application provides a novel targeted delivery strategy for overcoming the toxic side effects and tumor drug resistance of gemcitabine.

The invention provides a method for detecting insulin sensitivity, which comprises the following steps: (1) transfecting a cell to be detected by using a GLUT4myc cDNA plasmid: transfecting the cell to be detected by using the GLUT4myc cDNA plasmid, so that the cell stably expresses GLUT4myc; (2) measuring the endocytosis rate of the GLUT4myc: performing endocytosis stimulation to enable the GLUT4myc combined with the anti-myc antibody to be endocytosed, and regularly detecting the amount of the GLUT4myc combined with the anti-myc antibody remained on the surface of the cell; (3) measuring the GLUT4myc exocytosis rate: performing exocytosis stimulation to enable the GLUT4myc combined with the anti-myc antibody in the cell to exocytosis, and regularly detecting the translocation amount of the GLUT4myc combined with the anti-myc antibody in the cell to the surface of the cell; (4) calculating the difference value between the GLUT4myc exocytosis rate and the GLUT4myc endocytosis rate, and calculating the insulin sensitivity according to the difference value; the insulin sensitivity evaluation method has the beneficial effects that the insulin sensitivity is evaluated by detecting the exocytosis and endocytosis rates of fat cells, muscle cells or peripheral blood lymphocytes GLUT4, so that early-stage diabetic patients can be identified, and the pathogenesis of diabetes mellitus can be researched.

Provided are an antibody targeting Trop2, an antibody-drug conjugate, and use thereof. The provided antibody targeting Trop2 is capable of specifically binding to a target cell expressing human Trop2, has high affinity with same, is capable of entering the cell by means of endocytosis and inhibiting tumor growth or progression, and can be used for treating, preventing, and ameliorating conditions in a subject associated with abnormal expression of Trop2 (e.g., breast cancer, urothelial carcinoma, and non-small cell lung cancer).

Provided are a novel bispecific antigen-binding antibody, an antigen-binding fragment thereof, and a Trop2 * HER2 bispecific antibody drug conjugate (Trop2 * HER2 Abs ADC) which comprise a Trop2-binding arm and an HER2-binding arm, are capable of simultaneously specifically binding to HER2 and Trop2, have a high binding affinity to HER2 and Trop2, can be endocytosed by cells expressing HER2 and / or Trop2, and can be used as an antigen-binding fragment of a Trop2 * HER2 bispecific antibody drug conjugate. Endocytosis of the two binding arms L has a synergistic effect; the Trop2 * HER2 Abs ADC can inhibit the growth of tumor cells expressing HER2 and / or Trop2 in vitro and in vivo, and the bispecific antibody can be used for preventing and treating human diseases related to HER2 and / or Trop2, such as cancers.

A C-terminal fragment of insulin-like growth factor binding protein 2 (IGFBP2) containing 3 cysteine residues has been shown to spontaneously self-assemble into nanotube (NT) structures. These NTs can encapsulate drugs during the assembly process and then deliver their cargo intracellularly following binding to interns and endocytosis. The integrin-dependence of this process is mediated by the presence of a naturally occurring RGD motif within the peptide sequence. A particular advantage of such NTs is that by encapsulating small molecule drugs, tissues are protected from their adverse effects. Here, the use of NTs to deliver small drugs and biologics across the blood-brain barrier (BBB) by penetrating the CNS and delivering their cargo is described.

To provide bifunctional compounds that can be used to promote or enhance the degradation of certain circulating proteins.SOLUTION: What is claimed is: A compound comprising Formula (I): [Ab] k' - [CON] h - [Linker] I - [CON] h' - [CRBM] j' (I) wherein: Ab is an antibody that binds to an extracellular protein; CRBM is a cell receptor binding moiety that binds to at least one receptor on the surface of a degradative cell in a subject; (I) thereby results in endocytosis and degradation of the extracellular protein; each CON is independently a bond or a group that covalently links the Ab to the CRBM, the Ab to the linker, and / or the linker to the CRBM; the linker is a group having a valence ranging from 1 to 15; k ' is an integer ranging from 1 to 15; h is an integer ranging from 0 to 15; I is an integer ranging from 0 to 15; h ' is an integer ranging from 0 to 15; and j is an integer ranging from 1 to 15.SELECTED DRAWING: Figure 1

The application discloses a kind of Man-PFH-ICG@PLGA nanoparticles and preparation method and application thereof, belong to composite material preparation technical field.The application uses PLGA as carrier, using polylactic acid-glycolic acid (PLGA) nanoparticles (NPs) to mark the surface of it with mannose, and ICG and oxygen-carrying PFH are embedded therein, the obtained Man-PFH-ICG@PLGA nanoparticles have excellent targeting effect on the overexpression of mannose receptor on the surface of tumor cells, significantly promote the effective endocytosis of cells in vitro and tumor enrichment in vivo, directly relieve the hypoxic environment of tumor;It can also supplement oxygen by endogenous, to activate the TRPA1 channel overexpressed on the surface of tumor cells by ROS generated by cells, so as to inhibit cell respiration, reduce oxygen consumption, indirectly relieve the hypoxic environment of tumor, effectively inhibit the growth of tumor cells, and provide a new idea for clinical exploration of antitumor therapy.

The present application relates to the technical field of medicine, in particular to a kind of siRNA eye drop for penetrating mucus barrier and cell barrier and preparation method thereof.Innovative development side chain guanidino group-containing polydisulfide delivery carrier is used in the present application, through the quick dynamic disulfide exchange reaction between polydisulfide and sulfhydryl on mucin, tear film retention and efficient penetration are realized, and cationic polydisulfide is quickly adsorbed on the surface of negative charged cell membrane by electrostatic interaction, the quick dynamic disulfide exchange reaction between polydisulfide and sulfhydryl on cell membrane is used, and endocytosis is used to quickly penetrate tight junction cell layer.

The invention belongs to the technical field of immunotherapy, and particularly relates to a chimeric antigen receptor, separated nucleic acid, a recombinant vector, a CAR-T cell and application thereof. According to the CAR-T cell, the CAR efficiently circulates on the cell membrane through the specifically arranged intracellular domain, after antigen stimulation induces CAR endocytosis, the recyclable CAR can efficiently return to the surface of the cell, so that the CAR on the surface of the cell can be repeatedly and efficiently utilized, and the CAR-T cell has the advantages that the CAR-T cell has a good application prospect. Further research finds that the CAR-T cell with the recyclable CAR can more quickly remove tumor cells in vitro, and the treatment effect is better.

The invention provides an NPV linker sequence-based GD2 targeting antibody coupling drug, a preparation method and an application, and belongs to the technical field of biological medicines. According to the invention, an Asn-Pro-Val (NPV) sequence sensitive to neutrophil elastase is taken as a linker, and MMAE and Hu 3F8 are coupled by using a cysteine coupling technology, so that the antibody conjugate Hu 3F8-NPV-MMAE is obtained. The antibody conjugate shows good tumor cell killing ability, can significantly reduce the tumor volume, and is high in safety. And after passing through intercellular, the elastase of the antibody conjugate is split to release MMAE to play a role, so that the bystander effect can be enhanced, the curative effect of ADC can be improved, the drug-resistant mechanism related to ADC endocytosis and intracellular processing can be avoided, the enzyme specific splitting of Linker can be improved, and the toxic and side effects of ADC can be reduced.

The application provides an anti-ALPP / ALPPL2 antibody and application thereof, and belongs to the field of biological medicine. Specifically disclosed are an anti-ALPP / ALPPL2 antibody or an antigen binding fragment thereof, which comprises a heavy chain variable region CDR1, CDR2 and CDR3 sequence as shown in SEQ ID NO: 3, 4 and 5; and a light chain variable region CDR1, CDR2 and CDR3 sequence as shown in SEQ ID NO: 6, 7 and 8. The antibody has high specificity, high sensitivity and can mediate intracellular endocytosis.