35 results about "Endocytosis" patented technology

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 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.

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 belongs to the technical field of biological medicine and molecular biology, and particularly relates to a CAR-macrophage with enhanced efferocytosis targeting apoptotic cells and a preparation method and application thereof. The CAR provided by the application comprises a signal peptide segment, a ligand recognition domain, a tag gene, a hinge region, a transmembrane region and an intracellular signal domain, can recognize lipid or protein signals exposed on the surface of apoptotic cells in an inflammatory microenvironment, and realizes targeted phagocytosis and aggregation in an inflammatory area. DKP type unsaturated ionizable lipids have protonation characteristics in an acidic microenvironment, which helps mRNA encapsulation and endosome escape. Lipid nanoparticles contain CAR mRNA and can respond to broken surface ligands. Under inflammatory conditions, the ligands fall off to expose DOPS, thereby improving the endocytosis capacity of macrophages. The CAR-macrophage and the nanoparticles can be used to prepare drugs for treating diseases such as metabolic-associated fatty liver disease and atherosclerosis, realize multiple synergies, have high specificity and safety, and have good industrialization prospects.

The application relates to the technical field of nanomaterials, and particularly discloses a kind of nanomaterials for stem cell labeling and photoacoustic imaging, a preparation method and application thereof.The application provides a new method capable of stably labeling high-performance photoacoustic nanomaterials on the surface of stem cells in a quick, efficient, specific and non-damaging manner to cell functions, so as to realize high signal-to-noise ratio and long-term dynamic in-vivo tracing of stem cell transplantation fate, and overcome multiple limitations of traditional endocytosis labeling in efficiency, timeliness, specificity and cell compatibility.

This invention discloses a fluorinated membrane-fused liposome for modifying immune cells to regulate immunity, its preparation method, and its applications, belonging to the field of biomedical technology. This invention synthesizes a series of lipid molecules with different fluorinated chain lengths, including DOPE-F3, DOPE-F5, DOPE-F7, DOPE-F9, DOPE-F11, and DOPE-F13. Fluorinated membrane-fused liposomes are then prepared using these molecules in combination with other lipid components via a thin-film hydration method. These fluorinated membrane-fused liposomes exhibit excellent anti-protein adsorption capacity, efficient membrane fusion properties, and active spleen targeting. Experiments show that these fluorinated membrane-fused liposomes can achieve efficient membrane fusion with immune cells and effectively accumulate in the spleen in vivo, overcoming the shortcomings of traditional liposomes such as easy liver retention and low endocytosis efficiency. This invention has broad application prospects in the field of immunocellular therapy.

Provided are a targeting vector and a method for targeting same to a host cell. The vector comprises a first molecule that binds to an endocytosis receptor of the target cell and a second molecule that promotes the release of a substance carried by the targeting vector into a cytoplasm. When the targeting vector is a viral vector, the first molecule is not part of a viral envelope protein, and the second molecule promotes endosomal escape or lysosomal escape of the targeting vector. The first molecule is designed according to the endocytosis receptor of the cell to be targeted, different types of cells can be targeted, and after a reasonable mutation is carried out on the vector, infection of cells that do not need to be targeted can be avoided, thereby improving the accuracy of the vector.

An antibody or antigen-binding fragment thereof targeting ROR1 and a preparation method and application thereof, wherein the antibody or antigen-binding fragment thereof targeting ROR1 comprises a VL and a VH; the VL comprises CDRs or mutations thereof as shown in SEQ ID NO: 69, 78, 84 respectively, VL CDR1, VL CDR2, VL CDR3; and the VH comprises CDRs or mutations thereof as shown in SEQ ID NO: 12, 33, 53 respectively, VH CDR1, VH CDR2, VH CDR3. The above-mentioned antibody or antigen-binding fragment thereof has good binding affinity to ROR1; has little cross-reactivity with ROR2, and the KD values are comparable to those of the reference prior art antibodies; and has significant endocytosis and ADCC effect in tumor cells.

This invention discloses a high-BNIP3-loaded exosome, its preparation method, and its applications, relating to the field of biomedical engineering technology. The high-BNIP3-loaded exosomes are obtained by pre-treating human bone marrow mesenchymal stem cells transfected with a recombinant expression vector carrying the BNIP3 gene, followed by 24 hours of hypoxia at 1% oxygen concentration. The exosomes have a particle size of 40-130 nm and highly express BNIP3 and exosome markers HSP70, CD63, and TSG101. The preparation method includes constructing a pcDNA3.1-BNIP3 recombinant vector, transfecting and screening stable-expressing engineered cells, hypoxia pre-treatment, and purification by gradient centrifugation combined with ultracentrifugation. This invention achieves efficient loading and targeted delivery of BNIP3 through a synergistic strategy of genetic engineering and microenvironment simulation, significantly improving the endocytosis efficiency of nucleus pulposus cells, activating mitophagy, restoring mitochondrial function, and promoting extracellular matrix synthesis. It can be used to prepare drugs for treating intervertebral disc degeneration and has excellent clinical application prospects.

This invention relates to the field of biomedical technology. It provides a cardiac-targeting bispecific antibody protein and its applications. The bispecific antibody protein comprises a targeting conjugate that specifically recognizes NPR1 and a sequence that specifically recognizes GDF15. The amino acid sequence of the bispecific antibody protein is shown in SEQ ID NO.2. This invention cleverly achieves the dual functions of cardiac tissue targeting and effectively mediating endocytosis by utilizing a membrane protein specifically highly expressed in myocardial tissue as an effector molecule. The cardiac-targeting bispecific antibody protein of this invention can target the cardiac tissue surface receptor NPR1 and specifically target and degrade GDF15 within cardiac tissue, showing promising application prospects in the treatment of heart failure.

The present invention relates to bispecific antigen proteins that induce endocytosis and lysosomal degradation of PD-L1 when brought into contact with a cell expressing PD-L1 and RNF128. The invention further relates to the use of such bispecific antigen binding proteins in the treatment of cancer.

The application discloses a VirusTAC platform for tumor cell membrane protein PD-L1 or CD24 targeted degradation and application thereof, and belongs to the technical field of biological medicine. The platform comprises a heterodimer with R1-R2-R3 structure formed by a first polypeptide chain and a second polypeptide chain, wherein R1 is MeV H or a variant thereof; R2 is a linker composed of R4 and R5, R4 is an IgG Fc region; R5 is a linker that can be cut by a protease; and R3 is a target protein binding domain PD-L1 antibody or CD24 antibody. The platform can specifically recognize tumor high-expression receptors and induce rapid endocytosis of cells by means of tumor-specific expression and efficient endocytosis characteristics of Nectin-4, so as to overcome the defects of the existing TPD technology and realize effective regulation of various target proteins.

This invention specifically discloses an antibody targeting the endocytosis receptor TIMD-4 and its application in the preparation of drugs for treating atherosclerosis, belonging to the field of biomedical technology. The antibody provided by this invention can stabilize macrophage TIMD-4 by blocking the abnormal cleavage of TIMD-4, thereby restoring the phagocytic function of macrophages and enabling them to perform normal endocytosis. Experiments show that this antibody has therapeutic potential in treating atherosclerosis models.

This invention provides a bispecific antibody targeting tissue factors, an antibody-drug conjugate (ADC), its preparation method, and its application, belonging to the field of biopharmaceutical preparation technology. The bispecific antibody provided by this invention can efficiently target tissue factors in tumor cells, exhibiting advantages such as strong affinity and high endocytosis efficiency. This invention also provides an ADC, which, under the action of the bispecific antibody, specifically binds to tumor surface antigens and is internalized into tumor cells, achieving precise drug delivery for antitumor drugs. The ADC provided by this invention exhibits good tumor-suppressing effects in both cell and animal models, and is non-toxic and harmless to animals, demonstrating excellent potential for cancer treatment.

This invention relates to a unit drug conjugate wherein a binding group capable of binding to another drug conjugate is further linked to a unit drug conjugate in which a target substance and a drug specifically binding to a target cell are linked together. When the unit drug conjugate according to the invention is administered sequentially in vivo, the complex forms clusters through in vivo cross-linking, and these clusters promote endocytosis of the drug conjugate, thereby significantly enhancing the cellular internalization of the drug contained in the drug conjugate.

The application discloses a kind of bispecific antibody drug conjugates and its preparation method and purposes, and wherein, the structure of the bispecific antibody drug conjugates includes the following fragments: the bispecific antibody or its antigen binding fragment of anti-B7H3 and PD-L1, linker unit L and cytotoxic drug.The bispecific antibody drug conjugates of the application has good endocytosis effect, multiplication inhibitory activity and tumor growth inhibitory activity.

This invention discloses a sodium caseinate-based Pickering emulsion, its preparation method, and its application, belonging to the field of vaccine adjuvant technology. This invention is the first to propose using Salmonella Typhimurium flagellin and sodium caseinate as raw materials to formulate a Pickering emulsion. The prepared Pickering emulsion has the characteristics of small particle size, good biocompatibility, and high stability, and can induce a high immune response in the body. This invention is also the first to propose the application of the Pickering emulsion formulated using Salmonella Typhimurium flagellin and sodium caseinate as raw materials as a vaccine adjuvant. The Pickering emulsion prepared by this invention has a simple preparation process, requiring only mixing and homogenization, and can effectively load the model antigen OVA. This emulsion has good cellular safety and can promote the endocytosis of exogenous antigens by macrophages. The emulsion can induce the body to produce high levels of antibody titers, with antibody titers reaching more than 120,000 times.

The application relates to the field of biological medicine, and discloses an siRNA drug delivery system, a preparation method and application thereof. The siRNA drug delivery system contains a linker formed by co-assembly of a fusion protein and an siRNA drug, the fusion protein contains a substrate peptide, an endosome fusion peptide, an antibody for targeting a cell surface antigen, and a label protein connected with the siRNA drug. The preparation method of the siRNA drug delivery system comprises the following steps: mixing the fusion protein with the siRNA drug to perform reaction I, wherein the fusion protein contains a substrate peptide, an endosome fusion peptide, an antibody for targeting a cell surface antigen, and a label protein for being connected with the siRNA drug. The system can realize the targeted delivery and site-specific release of the siRNA, can realize the high-efficiency endocytosis of nucleic acid drugs, and finally improves the treatment effect.

This invention relates to a polymeric probe for assessing sialylation levels in vivo. It uses a dendritic polymer with alkyne-terminated branches as a carrier, and its surface is simultaneously modified with galactose, cyanidin 5 fluorescent dye, and folic acid. The detection protocol involves subcutaneously injecting the prepared polymeric probe into the tumor region of tumor-bearing mice. Folic acid-mediated targeted endocytosis allows the polymeric probe to enter the tumor cells. In vivo sialylates bind sialic acid to the galactose terminal of the polymeric probe. Sodium periodate is used to oxidize the sialic acid terminal in mouse tumor tissue sections to form an aldehyde group, which is then further coupled with an acylhydrazide fluorescein molecule. Fluorescence signals from cyanidin 5 and fluorescein are simultaneously collected using fluorescence microscopy, and the fluorescence intensity of fluorescein in the superimposed region of the two fluorescence signals is obtained using software, which can then be used to assess the sialylation level of the tumor tissue.

This invention discloses the preparation and application of a hydrophobic compound high-encapsulation protein carrier, belonging to the field of bionanomaterials and food functional factor delivery technology. This invention provides a hydrophobic lumen-modified ferritin mutant rXHF, obtained by mutating polar residues at positions 68, 76, 141, and 148 on the lumen surface of human heavy chain ferritin rHuHF to tryptophan. Using this mutant as a carrier, lycopene is compounded with lycopene at a molar ratio of 1:200 to prepare the lycopene nanodelivery system rXHF-LYC. This system has a lycopene encapsulation efficiency of 17.8% and a DPPH clearance rate of 30%. Through transferrin receptor-mediated endocytosis, it crosses the blood-brain barrier, delivering lycopene to the hippocampus, inhibiting oxidative stress and neuroinflammation, restoring cholinergic function, and improving age-related cognitive impairment. This invention provides a new carrier for brain-targeted delivery of hydrophobic functional factors and offers a new strategy for the intervention of age-related neurodegenerative diseases.

The application discloses a kind of lipid nanoparticle complex and its preparation method and application, belong to molecular biology technical field.The method includes: after CdSe / ZnS quantum dot is treated by removing oleic acid ligand, with mercapto seven glycol monomethyl ether reaction, methoxyl polyethylene glycol modified water-soluble quantum dot is obtained;The water-soluble quantum dot is mixed with multi-thiol phosphonate single-stranded DNA, and DNA-quantum dot complex is formed;The DNA-quantum dot complex is mixed with complex lipid by microfluidic, and lipid nanoparticle complex is formed.The quantum dot of the application is encapsulated in the interior of lipid nanoparticle, avoids the interference of surface marker to the original property of nanoparticle, combines super-resolution imaging and single particle tracking technology, realizes real-time observation and analysis to single lipid nanoparticle transmembrane movement process under nanometer scale, and can be used for lipid nanoparticle formula screening, nucleic acid drug delivery efficiency evaluation and intracellular endocytosis mechanism research.

The application discloses a VirusTAC platform for targeted degradation of tumor cell membrane protein EGFR and psoriasis extracellular pathogenic factor IL17A and application thereof, and belongs to the technical field of biological medicine. The platform comprises a heterodimer with R1-R2-R3 structure formed by a first polypeptide chain and a second polypeptide chain, wherein R1 is MeV H or a variant thereof; R2 is a linker composed of R4 and R5, R4 is an immunoglobulin Fc region, the Fc regions corresponding to the first polypeptide chain and the second polypeptide chain are associated by heterodimerization mutation; R5 is a linker that can be cut by a protease; and R3 is a target protein binding domain EGFR antibody or IL17A antibody. The platform realizes precise degradation of tumor-related membrane proteins and extracellular proteins by constructing a chimera of a natural ligand and a targeting antibody, and by means of tumor-specific expression and efficient endocytosis characteristics of Nectin-4.

This invention relates to the fields of biomedical engineering and nanomedicine delivery technology, specifically disclosing a homologous membrane nano-targeted drug delivery system for treating acute kidney injury with sepsis. The system includes: preparation of solid silicon spheres; mesoporization and etching; drug loading; preparation of homologous cell membranes; encapsulation and fusion; characterization and quality control. This invention utilizes KTP-modified RBCM vesicles to provide homologous surface proteins / receptors, achieving highly selective recognition and endocytosis of renal tubular cells, significantly improving drug accumulation and bioavailability in diseased kidney tissue, thereby enhancing therapeutic efficacy and reducing systemic exposure. The hollow, mesoporous structure provides high drug loading capacity and controllable release sites. The outer homologous membrane inhibits early leakage under physiological conditions and promotes drug release in inflammatory, acidic microenvironments, or intracellular environments, combining the advantages of sustained release and targeted activation.

The present application relates to the technical field of biological medicine. The present application provides a kind of targeted degradation protein and its application, the amino acid sequence of the targeted degradation protein is as shown in SEQ ID NO.3.The targeted degradation protein of the present application can actively mediate the endocytosis and degradation process of target protein based on extracellular protein targeted degradation technology, reduce the abundance of target protein from the source, so as to more fundamentally weaken its biological effect. Only need to screen or develop the binding molecule with high affinity to target protein, it can trigger its degradation. Significantly reduce the design difficulty, and greatly expand the range of target protein that can be intervened.

Application of a multifunctional supramolecular nanoplatform drug: The application of a multifunctional supramolecular nanoplatform in the preparation of drugs for liver ischemia-reperfusion injury. The multifunctional supramolecular nanoplatform is a GalAC4A supramolecular carrier loaded with naringenin (NAR). The multifunctional supramolecular nanoplatform is prepared from naringenin (NAR), galactose (Gal), and CAC4A from azocalixarene. The multifunctional supramolecular nanoplatform is a NAR@GalAC4A nanocomposite. The multifunctional supramolecular nanoplatform achieves hepatocyte-specific targeting through desialyl glycoprotein receptor-mediated endocytosis. This invention proposes a novel "receptor recognition-hypoxia response-synergistic therapy" three-pronged design strategy, successfully constructing a GalAC4A supramolecular carrier loaded with naringenin (NAR) to form a NAR@GalAC4A nanocomposite.

The present application relates to a kind of pharmaceutical composition for enhancing the efficacy of CAR-T cell, the pharmaceutical composition includes therapeutically effective amount of lysosomal inhibitor and pharmaceutically acceptable carrier.The present application first proposes and verifies by adjusting the endocytosis post-transport pathway of tumor cell itself, can overcome its CD4 + Resistance of CAR-T cell therapy provides new strategies for solving the heterogeneity of CAR-T therapy efficacy;The lysosomal inhibitor used is a drug that has been clinically used, and its safety is relatively clear, and CD4 + The clinical transformation potential of CAR-T cell combination therapy is large, and can be quickly applied to existing CAR-T treatment plan.

The present invention relates to the technical field of pharmaceuticals, and specifically relates to a polypeptide specifically binding to GPC3, and a drug conjugate thereof and the use thereof. The polypeptide has an amino acid sequence as shown in general formula (I), and the structure of the polypeptide-drug conjugate is as shown in general formula (1). Experimental results demonstrate that the polypeptide and polypeptide conjugate of the present invention that specifically bind to GPC3 exhibit high affinity, have a good internalization effect on cells with high GPC3 expression, can serve as candidate targeting molecules for anti-tumor drugs, and can be used for treating or diagnosing cancers associated with abnormal activation of the GPC3 target.

This invention discloses a nanobody-conjugated toxin reagent for detecting antibody endocytosis and internalization efficiency, its preparation method, and its application, belonging to the field of biopharmaceutical technology. This invention provides an alpaca-derived nanobody, whose amino acid sequence is shown in SEQ ID NO:1, and its CDR region is shown in SEQ ID NO:2-4. This nanobody binds with high specificity to the Fc fragment of human IgG1 / IgG4, and after conjugation with a toxin drug, forms the nanobody-conjugated toxin reagent HK-D4-MMAE. This reagent has a small molecular weight, high affinity, stable complex, a DAR value up to 4, and is non-cytotoxic within the working concentration range. After binding to the antibody to be tested, it has virtually no impact on its internalization process. The method for detecting antibody endocytosis and internalization efficiency using this reagent is simple to operate, yields accurate results, and is comparable to the internalization effect of real ADC drugs. It can be used for screening and evaluating the internalization efficiency of large quantities of antibodies in the early stages of ADC drug development, showing promising application prospects.

This invention discloses a brain delivery nanocarrier via a transcellular transport pathway. It uses a lecithin-modified inorganic nanomaterial as its core and a membrane-fused liposome-cell membrane as its shell. The membrane-fused liposome-cell membrane coats the surface of the lecithin-modified inorganic nanomaterial, forming a core-shell structure. The membrane-fused liposome-cell membrane is formed by the hybridization and fusion of membrane-fused liposomes with the cell membranes of metastatic brain cancer cells. This brain delivery nanocarrier can efficiently cross the blood-brain barrier via a membrane fusion pathway, bypassing the classic endocytosis-lysosome pathway to enter brain microvascular endothelial cells, thus solving the problems of low delivery efficiency and easy retention and degradation in lysosomes of existing nanomaterials.