1016 results about "Lysosome" patented technology

The invention relates to the technical field of nano delivery carriers, in particular to an ionizable lipid compound with a three-dimensional space structure and a preparation method and application thereof. The ionizable lipid compound provided by the invention comprises a three-dimensional space structure constructed by a polar head group, a connecting bond and a hydrophobic tail. Diversified ionizable lipid compounds with different three-dimensional space structures are constructed by changing various polar head groups, connecting bonds and hydrophobic tails contained in an ionizable lipid compound combinatorial library, and the ionizable lipid compounds have excellent mRNA (messenger ribonucleic acid) binding capacity. The invention also provides preparation and application of the ionizable lipid compound with the advantageous three-dimensional space structure. The novel ionizable lipid compound with an advantageous three-dimensional space structure has stronger binding capacity with mRNA, and lipid nanoparticles synthesized from the novel ionizable lipid compound have excellent physicochemical characteristics, high cell uptake rate, lysosome escape rate and cell and in-vivo transfection rate, and have the function of specifically targeting liver, spleen or lung.

The invention relates to a drug delivery carrier based on extracellular vesicles and application thereof.The drug delivery carrier contains extracellular vesicle scaffold protein and recombinant membrane fusion protein, the recombinant membrane fusion protein comprises a first fragment and a second fragment, the amino acid sequence of the first fragment is shown as SEQ ID NO: 5, and the amino acid sequence of the second fragment is shown as SEQ ID NO: 6; the second fragment has n amino acids, the sequence of the second fragment is the sequence of the first n amino acids at the N end of the amino acid sequence as shown in SEQ ID NO: 7, and n is an integer between 50 and 200. According to the drug delivery carrier disclosed by the invention, the efficiency of releasing drug active molecules before reaching lysosome is remarkably improved, and the drug effect of extracellular vesicle drugs can be improved.

The invention provides a membrane protein targeted degradation agent based on cell autophagy, the degradation agent has a first structure combined with membrane protein and also has a second structure capable of inducing cell autophagy, and the first structure is connected with the second structure. According to the membrane protein targeted degradation agent based on cell autophagy, the cell autophagy mechanism is utilized for membrane protein degradation for the first time, due to the fact that autophagy is an internal mechanism of various cells, universal induction can be achieved in various cells, and the autophagy does not depend on factors such as lysosome transporter protein and E3 ligase on cell membranes; the method has the characteristics of broad spectrum and higher universality; the design route of direct connection of the first structure and the second structure is simple and easy to realize.

The present disclosure provides oligonucleotides, methods, and compositions for degrading RNA via the lysosomal pathway. Also contemplated are oligonucleotides, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with EXOC2, Ku80, and Task1 in a subject in need thereof.

The invention discloses a PEI and targeting peptide modified magnetic nano-carrier and a preparation method and application thereof. The nano-carrier is regular in morphology and uniform in particle size and has good crystallinity and magnetic performance. E5 polypeptide and RGD cyclic peptide on the surface of the nano-carrier are respectively combined with CXCR4 protein and integrin on the surface of a tumor cell, and the nano-carrier and CXCR4 are internalized into lysosome through an integrin-mediated way, so that the target protein CXCR4 is degraded. The PEI in the nano-carrier can load and deliver siRNA into tumor cells to silence the expression of CXCR4 mRNA (messenger Ribonucleic Acid). Through nucleic acid delivery and a protein targeted degradation strategy, the CXCR4 level of tumor cells is jointly reduced, the migration ability of the tumor cells is inhibited, and meanwhile, the anti-tumor effect of M1 type polarization of macrophages is activated.

The invention relates to dithiolane modified beta-cyclodextrin, a preparation method thereof and application of the dithiolane modified beta-cyclodextrin as a drug carrier. The method comprises the following steps: carrying out acylation reaction on beta-cyclodextrin and lipoic acid, and modifying different numbers of dithiolane on the beta-cyclodextrin by changing a feeding ratio; the beta-cyclodextrin has a plurality of hydroxyl groups, and the activity of the hydroxyl groups at the C6 position is relatively high. The hydrophobic cavity of the dithiolane-modified beta-cyclodextrin can be loaded with a hydrophobic small-molecule drug, and the hydrophobic small-molecule drug can be loaded into the dithiolane-modified beta-cyclodextrin under the condition of heating reflux to form a nano-drug. The disulfide bond on the surface of the nano-drug and sulfydryl on protein or lipid on the outer side of a cell membrane are subjected to dynamic covalent thiol exchange, so that the nano-drug enters cells through a thiol-mediated cellular uptake way, endosomes and lysosomes can be avoided, the drug is quickly and directly delivered to the cytoplasm, degradation of the drug in the lysosomes is reduced, and the drug delivery efficiency is improved. The utilization rate of small-molecule drugs is improved, side effects are reduced, and better curative effects are achieved.

The invention belongs to the field of biological medicines, and discloses an application of a stem cell extract in lysosome and mitochondrial related diseases, a preparation method of the stem cell extract comprises the following steps: S1) culturing mesenchymal stem cells and creating stress conditions to stimulate the mesenchymal stem cells; and S2) separating and purifying the culture supernatant of the mesenchymal stem cells cultured in the step S1) to obtain the stem cell extract, wherein S21) the culture supernatant is filtered to obtain a filtrate; s22) performing 3KD ultrafiltration concentration on the filtrate to obtain a crude sample; s23) purifying the crude sample by using molecular sieve exclusion chromatography or reversed-phase chromatography to prepare a purified sample; in molecular sieve exclusion chromatography, by taking the volume of the eluent as a reference, collecting the 10th to 40th mL of eluent, namely a purified sample; and S24) taking the purified sample to form a preparation. According to the application, the culture supernatant containing stress stem cell secretions is taken through stress culture of stem cells, and a purification method is combined, so that the prepared preparation can be used for treating lysosome and mitochondrial related diseases.

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 invention discloses novel application of notoginsenoside Rg1, namely application of the notoginsenoside Rg1 in preparation of a cathepsin D (CTSD) inhibitor, the notoginsenoside Rg1 can inhibit CTSD enzyme activity so as to recover lysosome structure and function, relieve endoplasmic reticulum stress reaction and relieve alpha-syn aggregation and dopaminergic neuron apoptosis, has a remarkable protection effect on a Parkinson's disease model, and can be used for preparing a novel anti-inflammatory drug. The invention provides a new thought and a potential drug basis for targeted intervention of Parkinson's disease. The invention discloses a new mechanism that Rg1 plays a role in neuroprotection through a CTSD-lysosome-endoplasmic reticulum stress pathway.

The invention belongs to the field of biomedical materials, and particularly relates to a PBAE-DOPE-PEG2000 polymer-lipid nanocomposite and a preparation method and application thereof.The preparation method comprises the steps that a dimethyl sulfoxide-ethanol solution formed by mixing DOPE-PEG2000 lipid and PBAE serves as an oil phase, a sodium acetate / acetic acid buffer solution serves as a water phase, and the PBAE-DOPE-PEG2000 polymer-lipid nanocomposite is prepared through a microfluidic synthesis mode; the PBAE-DOPE-PEG2000 polymer-lipid nano composite material is prepared by the steps of carrying out ultrasonic treatment on the PBAE-DOPE-PEG The polymer-lipid nano composite material can efficiently load exogenous genes, the surface performance of the polymer-lipid nano composite material is changed and the stability of nano particles is improved by introducing DOPE-PEG2000 lipid, membrane fusion can be promoted, the risk of lysosome degradation is reduced, the transfection process of the exogenous genes in recipient cells is accelerated, and efficient expression in 293FT cells is realized. The efficient transfection of the polymer-lipid nanocomposite material is expected to show important application prospects in immune cell therapy or tumor cell therapy.

The invention discloses a preparation method and application of a QS-21-polyamino acid nano vaccine, and belongs to the field of biomedical nano materials. The preparation method comprises the following steps: modifying gamma-PGA with phenylalanine ethyl ester (F) to obtain a polymer PF40 of which the F grafting rate is 40%; aiming at the characteristic that QS-21 is strongly combined with cholesterol, PF40 (PFC) grafted with cholesterol (C) is developed, and PFC wraps OVA and QS-21 through hydrophobic force to construct a nano vaccine OQPFC. The cholesterol on the PFC can reduce the combination of the QS-21 and the cholesterol on a cell membrane so as to reduce the biotoxicity of the QS-21, and the QS-21 loading efficiency of the nano vaccine is improved, so that a better treatment effect is achieved. The OQPFC can escape from lysosome through carboxyl protonation, and a large amount of QS-21 and OVA are released in cytoplasm, so that the synergistic cellular immune activation effect of the carrier adjuvant PFC and the saponin adjuvant QS-21 is realized.

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.

Aspects of the disclosure relate to complexes comprising an anti-TfR1 antibody covalently linked (e.g., via a linker such as a peptide linker) to a lysosomal enzyme (e.g., an acid alpha glucosidase enzyme), and methods of making and using the fusion complexes to treat a lysosomal storage disease (e.g., Pompe disease).

The invention discloses application of a lysosome cathepsin L inhibitor in a medicine for treating or relieving allergic airway inflammation, and relates to the field of allergic airway inflammation. It is found through research that inflammatory response of asthma can be relieved by inhibiting expression of lysosome CTSL in macrophages and animal models; the inflammatory response of asthma can be relieved by inhibiting expression of lysosome CTSL in macrophages by using a small-molecule inhibitor and myeloid specific knockout CTSL, so that the lysosome cathepsin L inhibitor can effectively relieve allergic airway inflammation, and a new direction can be provided for research and development of drugs for treating and relieving allergic airway inflammation in the future.

The invention relates to inhibitors of glucosylceramide synthase (GCS) useful for the treatment of metabolic diseases, such as lysosomal storage diseases, either alone or in combination with enzyme replacement therapy, cystic disease and for the treatment of cancer.

The invention belongs to the field of biological medicines, and relates to a drug-loaded nano-vesicle as well as a preparation method and application thereof. The drug-loaded nano-vesicle comprises a vesicle core and a drug-loaded nano-vesicle, wherein the vesicle core comprises siRNA (small interfering Ribonucleic Acid) capable of specifically targeting and silencing an NR1D1 gene; the vesicle membrane is formed by fusing an erythrocyte membrane, a macrophage membrane, cardiolipin, cholesterol and lecithin. The drug-loaded nano-vesicle can specifically target macrophages in a sepsis immunosuppression stage, has an intracellular response release function, recovers BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axis functions by inhibiting NR1D1 expression, reconstructs a macrophage phagocytosis function and lysosome-dependent bacterium removal capability, and can be used for preparing a drug-loaded nano-vesicle with a specific targeting function. The survival rate of sepsis immunosuppression model animals is obviously improved; and the bacterial load is reduced. Compared with a traditional electroporation method, the preparation method disclosed by the invention has the advantage that the encapsulation efficiency of siRNA is remarkably improved.

The invention discloses a sulfatase-driven polypeptide condensate with a chemotherapy sensitization effect and a preparation method thereof, and belongs to the field of biological medicines. According to the principle that sulfatase can catalyze hydrolysis of sulfate bonds, main polypeptide YSO4F responded by sulfatase enzyme is designed and synthesized; and the enzyme response aggregate m-YSO4F-LSG is blended with a protein G3BP2 ligand FGDF-YSO4F to prepare the enzyme response aggregate m-YSO4F-LSG with a sorafenib chemosensitization effect. Tumor cells can generate stress particles with a chemotherapy drug resistance effect under the stimulation of a chemotherapy drug sorafenib, the treatment effect of the sorafenib is weakened, and the protein G3BP2 is one of core proteins of the stress particles. After the m-YSO4F-LSG enters tumor cells, sulfate groups are hydrolyzed under the catalytic action of sulfatase overexpressed in tumor cell lysosomes, so that phase separation liquid drops d-YF-LSG with high affinity to protein G3BP2 are formed in the cells in situ, the phase separation liquid drops d-YF-LSG act with the protein G3BP2 and are fused with stress particles, chemotherapy drug resistance generated by the stress particles is inhibited, and the chemotherapy effect is improved. The treatment effect is improved.

[Problem] To provide a novel ferroptosis-inducing drug, and in particular, to provide a ferroptosis induction promoter that can effectively promote the induction of ferroptosis even in a cell having ferroptosis resistance even in a ferroptosis-inducing environment (for example, cancer cells and senescent cells). [Solution] Provided is a ferroptosis induction promoter comprising a drug that can reduce lysosomal pH.

The present disclosure relates, in part, to compounds of the Formula (I): (Formula (I)) or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein the variables are as defined herein. Also provided are compositions comprising said compounds and methods of use for treating certain diseases or disorders, including, for example, neurodegenerative diseases and lysosomal storage diseases.

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 a blood analyzer, a blood analysis method, a cell analysis reagent and application. The blood analyzer comprises: a sample suction device for sucking a blood sample to be detected; the sample preparation device is used for preparing a first sample and comprises a reaction tank for mixing at least one part of a blood sample to be detected with a first reagent comprising a first hemolytic agent and a lysosome staining agent containing a lysosome dye; the optical detector is used for detecting the first sample to obtain a first optical signal. The processor executes the following steps: processing the first optical signal to obtain first leukocyte information; extracting at least one first leukocyte parameter of the first leukocyte information; and obtaining an infection marker parameter based on the at least one first leukocyte parameter.

The invention belongs to the field of nano biomedicine, and particularly discloses a yeast bionic vaccine based on a metal organic framework ZIF-8 as well as a construction method and application of the yeast bionic vaccine, and the structure of the bionic vaccine is that ZIF-8 loaded with antigen OVA is encapsulated in a yeast shell. The invention relates to preparation and anti-tumor immune response of the bionic vaccine. The yeast shell is obtained by performing acid and alkali treatment and organic solvent washing on saccharomycetes and has the effects of targeting antigen presenting cells and stimulating immune response, and the antigen-loaded metal organic framework ZIF-8 is encapsulated in the yeast shell and has relatively good stability and an effect of continuously releasing antigens. The ZIF-8 is decomposed in antigen presenting cells, and lysosome escape of the antigen is induced. The yeast bionic vaccine provided by the invention can specifically target antigen presenting cells, continuously release tumor antigens in vivo, mediate escape of lysosome of the antigens and stimulate strong anti-tumor immune response, and has a better application prospect.

The invention belongs to the technical field of biological medicine, and particularly relates to an LYTAC molecule for targeted degradation of GPC3 and a preparation method and application of the LYTAC molecule. The LYTAC molecule is composed of a target TfR1 nucleic acid aptamer and a target GPC3 nucleic acid aptamer, wherein the nucleotide sequence of the targeted TfR1 nucleic acid aptamer is as shown in SEQ ID NO: 1; the nucleotide sequence of the targeted GPC3 nucleic acid aptamer is as shown in SEQ ID NO: 2. According to the present invention, the research results show that the GPC3 protein content is not affected by the single TfR1 nucleic acid aptamer or the GPC3 nucleic acid aptamer, and the LYTAC molecule can significantly reduce the GPC3 protein content on the surfaces of Hep3B and HepG2 cells. The LYTAC molecule induces GPC3 protein degradation through a lysosome way, then proliferation and migration of liver cancer cells are inhibited, liver cancer treatment is achieved, and the LYTAC molecule has wide application prospects.

The invention discloses a double-selenium lipid nanoparticle as well as a preparation method and application thereof. According to the nanoparticle, a skeleton is composed of cationic lipid, neutral phospholipid, cholesterol and functionalized PEG lipid, meanwhile, mRNA and a TLR agonist for coding therapeutic protein are carried, and the nanoparticle is synthesized through an ethanol injection method; the nanoparticle has both active targeting and strong transfection capabilities, the lipid nanoparticle is actively targeted to a tumor microenvironment and is taken by tumor cells by using biotin modified PEG lipid, and rapid'inclusion-lysosome 'escape is realized in the tumor cells by using trifluorogroup modified PEG lipid. Meanwhile, the nanoparticles are degraded in a glutathione / hydrogen peroxide dual-mode, so that the entrapped medicine is quickly and effectively released; the drug delivery system provided by the invention is simple in synthesis method, high in gene transfection efficiency and good in biological safety, and has potential value in anti-tumor research and clinical application.

The present invention relates to methods and products for assessing autophagic flux, and more specifically provides a biochemical functional measure used to quantify autophagic flux in sub-populations of blood cells. The present invention also provides lysosomal system markers for use in the methods described herein, systems for assessing autophagic flux, methods of identifying markers indicative of autophagic flux, and methods of treating subjects found to be suffering from, or susceptible to, a disease, condition or state associated with autophagic flux dysfunction using the methods described herein.

The invention relates to the cross technical field of biological medicine and image processing, and discloses a mesenchymal stem cell aging detection method based on image processing. The method comprises the following steps: automatically collecting bright field and multi-channel fluorescence images in an integrated cell culture monitoring device; after background correction and illumination homogenization, segmenting the cells by using a U-Net network and extracting single cell contours; calculating characteristics such as cell area, roundness, cytoplasmic ratio, nuclear form irregularity index, lysosome fluorescence intensity mean value and distribution entropy; and inputting a gradient boosting decision tree model to judge the unicellular aging state, and evaluating population aging with a 20% positive rate threshold. According to the invention, label-free, non-invasive and high-flux accurate detection is realized, and the method is superior to manual interpretation.

The invention discloses a galactose-masked aminoquinoline compound and application thereof, the structural formula of the galactose-masked aminoquinoline compound is # imgabs0, and R is acetyl, propionyl or butyryl. After being subjected to hydrolysis deacetylation, propionylation or butyrylation by esterase in cells, the compound can be activated by senescence-related beta galactosidase in senescence cell lysosome to release aminoquinoline (NCQ) so as to inhibit the survival of senescence cells in vivo or in vitro.

The present disclosure relates to harnessing endosomal sorting of lipids to enable targeted protein degradation via the lysosomal degradation pathway. Accordingly, provided herein are molecules for degrading target proteins, pharmaceutical compositions of such molecules, and methods of making and using such molecules.

[Problem] To provide a pharmaceutical composition containing a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, which is stable enough to permit its distribution to the market.[Solution] A lyophilized formulation containing; a fusion protein comprising an antibody and a lysosomal enzyme as an active ingredient, and further containing a neutral salt, a disaccharide, a nonionic surfactant, and a buffer. Such a lyophilized formulation includes, for example, as an active ingredient, a fusion protein comprising an anti-transferrin receptor antibody and human iduronate-2-sulfatase, and further containing sodium chloride as the neutral salt, sucrose as the disaccharide, poloxamer as the nonionic surfactant, and phosphate buffer as the buffer.