191 results about "Endocytosis" patented technology

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 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.

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 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 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 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 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.

The invention relates to the technical field of biomedicine, in particular to a preparation method of sequential targeting mesoporous manganese oxide nano-enzyme and application of the sequential targeting mesoporous manganese oxide nano-enzyme in treatment of ischemia reperfusion induced acute kidney injury. Adding a potassium permanganate solution into the silicon dioxide nanoparticle dispersion liquid under ultrasonic waves, and carrying out alkali etching to obtain mesoporous manganese oxide nanoparticles (HMN); and after surface amination modification, connecting with a mixed PEG spacer layer, and reacting with thiolated SS31 and azidoacyl hyaluronic acid to obtain the nano-enzyme. The preparation can effectively penetrate through a damaged glomerulus filtration barrier and is passively enriched in a damaged kidney, damaged renal tubular epithelial cells over-express CD44 receptor mediated hyaluronic acid modified nano-particle endocytosis is enhanced, SS31 modified nano-particles achieve lysosome escape mitochondrial targeting in cells, the level of active oxygen in mitochondria can be reduced, and the activity of the mitochondria can be improved. The mitochondrial function is recovered, the renal function and tissue pathological injury are improved, and accurate anti-oxidation treatment on the acute kidney injury is realized.

A nanoparticle and a preparation method therefor, the nanoparticle including an amphiphilic peptide, which forms a micelle structure through self-assembly, and a target peptide (preferably, a water-soluble antigen peptide), which electrically binds to the surface of the amphiphilic peptide. The target peptide electrically binds to the surface of the amphiphilic peptide micelle structure and becomes particulated, and thus can be effectively presented to an antigen-presenting cell, and the weight ratio of the amphiphilic peptide and the target peptide is controlled so that the size of nanoparticles is controlled and endocytosis thereof is carried out, and thus immunity by means of cytotoxic T cells can be induced. Nanoparticles exhibit use only an epitope of a more accurate region so as to be effective as a vaccine, and thus have minimal side effects. Therefore, excellent antigen-specific antibody and cell immunotherapy effects are exhibited, and thus can be used in various fields such as vaccine production.

The application belongs to the technical field of biology and particularly relates to a functional recombinant Cas9 protein targeted to an ovocyte of Procambarus clarkii and application thereof. The protein is NLs-VgSP-Cas9-NLs. The application directly delivers the recombinant Cas9 protein, thereby reducing the risk of integration of exogenous genes. By specifically targeting the ovocyte, off-target effects on somatic cells can be avoided, the efficiency of editing of germ cells is improved, and early development or genetic manipulation can be conveniently studied. The ovocyte of Procambarus clarkii is large, the recombinant Cas9 protein is efficiently delivered by receptor-mediated endocytosis on the surface of the ovocyte, and the problem that microinjection of zygotes cannot be implemented is solved.

The invention provides an active targeting nano-carrier as well as a preparation method and application thereof, and belongs to the technical field of nano-drugs. HA and NH2-PP are mixed and subjected to a coupling reaction to obtain an active targeting nano-carrier, the active targeting nano-carrier forms a nano-particle with a core-shell structure in an aqueous solution through self-assembly, and the nano-particle has two independent spaces with great polarity difference, so that the active targeting nano-carrier can be used for preparing a nano-particle with a core-shell structure. An inner core is an extremely hydrophobic space constructed by polylactic acid-glycolic acid and can be used for carrying hydrophobic drugs, an outer layer is a strong polar space taking polyethylene glycol as a main body and is beneficial to loading of hydrophilic drugs with strong polarity, so that synergistic loading of the hydrophilic and hydrophobic drugs is realized, and meanwhile, HA has specific binding and mediating endocytosis, so that the drug delivery efficiency is improved. Hydrophilic and hydrophobic drugs can be synergistically and accurately delivered to a tumor area, and the synergistic treatment effect of the two drugs is achieved.

Disclosed are: a fluorescent compound represented by general formula (I), (I)′, or (I)″, as a fluorescent compound which has high retention in a lipid bilayer, has excellent ease of handling, and can achieve uniform dyeing in a dyeing target; and a lipid bilayer dyeing method and an endocytosis detection method using said compound.Ch is a hydrophobic-field-sensitive fluorescent chromophore in which the fluorescence intensity increases in hydrophobic environments; A-H is an anionic functional group capable of generating anions by deprotonation; Xn+ is a positive ion having biological compatibility; n is 1, 2, or 3; L is a linker that binds to a hydrophobic-field-sensitive fluorescent chromophore and links the fluorescent chromophore and the anionic functional group; and LH+ indicates a state wherein the linker, which contains a cationic functional group capable of generating cations by protonation, has generated a cation by protonation.

Provided is relating to the field of disease treatment, and in particular, to an anti-CDH3 antibody or an antigen-binding fragment thereof, a nucleic acid molecule encoding the same and a method for preparing the same. The anti-CDH3 antibody or the antigen-binding fragment thereof has high affinity binding and endocytosis activities for CDH3, while exhibiting high specificity. Provided is furtherly relating to the use of the antibody or the antigen-binding fragment thereof in the treatment and diagnosis of diseases.

This application provides an NPQ-IgG2 / Fc fusion protein and its applications. The fusion protein comprises an NPQ polypeptide and a human IgG2 / Fc region. The NPQ-IgG2 / Fc fusion protein has the ability to specifically bind to hepatocyte HEPG2 and insulin-secreting cells INS-1, and after binding to cells, it undergoes endocytosis, activating intracellular signaling pathways. This application also discloses that the NPQ-IgG2 / Fc fusion protein, through multi-target effects including promoting hepatocyte glucose and lipid metabolism and improving pancreatic β-cell function, can be used to treat liver diseases including fatty liver, diabetes, and other metabolic diseases related to glucose or lipid metabolism disorders.

This invention provides a controlled-release pharmaceutical composition containing indigo naturalis or its main active ingredient, a method for its preparation, and its application. The controlled-release pharmaceutical composition comprises microspheres, each microsphere containing the active ingredient and one or more pharmaceutically acceptable excipients. The active ingredient includes indigo naturalis, indigo, indirubin, or any combination thereof; the microspheres are coated with an enteric outer layer. The controlled-release pharmaceutical composition provided by this invention can alleviate the symptoms of inflammatory bowel diseases, especially ulcerative colitis, and can reduce or avoid the endocytosis of the active ingredient by intestinal macrophages, thereby reducing the impact on the patient's liver. It exhibits good stability, and the controlled-release pharmaceutical composition of this invention reduces side effects while maintaining therapeutic efficacy.

The application discloses a HER2 antigen binding molecule and application thereof. The HER2 antigen binding molecule comprises at least one VHH chain, and the VHH chain comprises CDR1, CDR2 and CDR3, wherein the CDR1 comprises an amino acid sequence as shown in SEQ ID NO: 13, the CDR2 comprises an amino acid sequence as shown in SEQ ID NO: 14, and the CDR3 comprises an amino acid sequence as shown in SEQ ID NO: 15. The HER2 antigen binding molecule provided by the application shows a HER2 binding activity equivalent to that of trastuzumab and has a HER2 binding activity competitive with that of trastuzumab; and the HER2 antigen binding molecule provided by the application shows a better tumor cell killing effect through ADCC and endocytosis activity detection.

The invention discloses chloroindole hydrazide-loaded nanogel and a preparation method and application thereof, and relates to the technical field of pesticides, the chloroindole hydrazide-loaded nanogel is successfully prepared, CHI can be stably loaded, slow release is realized, and the chloroindole hydrazide-loaded nanogel has excellent leaf adhesiveness, can resist rain wash and avoid loss of pesticide effect, and can be used as a pesticide for preventing and treating diseases. The application pain point of CHI and the defects of a traditional nano-carrier are overcome; the nano-scale characteristic assists plant cell endocytosis and uptake, breaks through the transport limitation of cell membranes, and gives full play to the high induced resistance activity of CHI. High-speed centrifugal purification is not needed in the preparation process, the process is simplified, the yield is increased, large-scale production is adapted, and meanwhile energy consumption and cost are reduced. Compared with a traditional nano-carrier, the nano-gel does not need expensive precursors or complex modification, is good in dispersity and free of the agglomeration problem, preparation is low in energy consumption and pollution, the comprehensive performance is more suitable for practical application of pesticide carriers, and a solution with practicability and economical efficiency is provided for efficient prevention and treatment of plant virus diseases.