321 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 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.

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 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 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 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 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 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.

Described herein are compositions and methods for selective depletion of target molecules using a recyclable CDP-receptor-binding mediated complex to elicit endocytosis and cellular degradation of the target. Exemplary compositions containing a peptide, such as a CDP peptide, that bind a transferrin receptor can be linked to a peptide that binds a target molecule. Such compositions can be used to selectively recruit the target molecule to endosomes via transferrin receptor-mediated endocytosis of the composition and the bound target molecule. Once inside the endosome, the acidic pH can lead to release of the target molecule from the composition due to pH-dependent binding of the composition for the target molecule, and the transferrin receptor portion is recycled back to the cell surface for “reloading”. The target molecule can then be trafficked into lysosomes wherein it is degraded.

Disclosed are a metal-polyphenol nano-coating-wrapped tumor whole cell, a preparation method therefor, and use thereof. A plant polyphenol in the present invention and manganese ions can be rapidly assembled at room temperature to form a dense coating on the membrane of a tumor cell. The nano-coating wrapping inactivates the tumor cell, ensuring that the vaccine is safe. The nano-coating can prevent any potential tumor antigen from being lost under physiological conditions. The nano-coating is further modified with a lipopolysaccharide, which can promote the endocytosis of the formed whole-cell vaccine by antigen-presenting cells. While forming the structural coating, ions of the metal manganese can stimulate the STING pathway to enhance the anti-tumor 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.