59 results about "Lysosomal targeting" patented technology

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 discloses a lysosome targeted degradation system based on a DNA phase separation aggregate as well as a preparation method and application of the lysosome targeted degradation system, and belongs to the technical field of biological medicine and nanotechnology. The lysosome targeted degradation system based on the DNA phase separation aggregate comprises an RNA-DNA tetrahedral framework with a cohesive end, the RNA-DNA tetrahedral framework is formed by self-assembly of a core chain and an edge chain through complementary base pairing, the edge chain is a DNA-RNA chimeric oligonucleotide chain, and the DNA-RNA chimeric oligonucleotide chain is a DNA-RNA chimeric oligonucleotide chain. One or more sections of RNA ribonucleotide sequences which can be specifically recognized and cut by RNase H enzyme are embedded in the sequence, and the tail end of the RNA ribonucleotide sequence is modified with a cohesive tail end for driving phase separation and a cell membrane anchoring group; the RNA-DNA tetrahedral framework is modified with an aptamer of a targeted membrane protein. After entering cells, the system is subjected to liquid-liquid phase separation in a lysosome acid environment through interaction of cohesive ends, a micron-sized large-size aggregate is formed in situ, the residence time of a nano-drug in the lysosome is prolonged, and efficient degradation of target membrane protein is realized.

This invention discloses a naphthimide-based fluorescent probe for detecting HClO and its preparation method. The fluorescent molecular probe uses naphthimide as the fluorophore and C=N as the specific reaction site for HClO. Due to the presence of the naphthimide fluorophore, the probe molecule exhibits two-photon properties, enabling deep tissue penetration, reducing background noise, and facilitating fluorescence imaging of biological systems. Furthermore, the introduced morpholine group allows for lysosomal targeting, enabling the monitoring of hypochlorous acid concentration levels in lysosomes, making it a valuable tool for early disease diagnosis. In addition, this type of probe molecule is simple to synthesize, operates under mild reaction conditions, exhibits stable optical properties, and has a high synthesis yield. It can detect a wide range of HClO, making it practically valuable in fields such as biochemistry and environmental science.

The invention relates to the technical field of biological medicine, in particular to application of hordenine in preparation of a lysosome targeting preparation. The hordenine can be captured by the lysosome and accumulated in the lysosome, so that the hordenine has the characteristic of targeting the lysosome, and the hordenine can be used for preparing the lysosome targeting preparation. Hordenine is small in toxic and side effects and high in safety, and the problems that existing lysosomal targeted compounds such as chloroquine are high in toxicity and narrow in therapeutic window are effectively solved.

The application discloses application of a lipoic acid analogue in preparation of a product for relieving myocardial cell hypertrophy, and the lipoic acid analogue DMAE-LA is N -(2-(dimethylamino)ethyl)-5-(1,2-dithiopentyl-3-yl)valeric amide. DMAE-LA can effectively reduce ISO-induced myocardial hypertrophy of mice, reduce heart weight index and ANP and BNP expression, and significantly improve heart function. A small dose (2-10 μM) of a lysosome-targeting lipoic acid analogue DMAE-LA can effectively improve Ang II-induced myocardial hypertrophy and oxidative stress in H9c2 cells, and the protective effect is better than that of a high dose (200-400 μM) of LA. As a new substitute of traditional LA, DMAE-LA shows great potential for prevention and treatment of cardiovascular diseases.

To provide a means capable of inducing decomposition of a new protein which can be comprehensively and generally used for all cells.SOLUTION: A peptide compound comprising a target-binding moiety, a cell membrane-penetrating peptide moiety, and a lysosome-inducing peptide moiety.SELECTED DRAWING: None

This invention relates to a lysosome-targeting fluorescent dye based on the BODIPY structure and its synthesis method, belonging to the field of organic fluorescent dyes. The invention designs and synthesizes the lysosome-targeting fluorescent dye BDP. The dye molecule uses BODIPY as the parent structure, and a novel lysosome-targeting fluorescent dye molecule is synthesized by introducing diphenylphosphine salt and tert-butyloxycarbonyl groups. The synthetic route of this dye is simple, it possesses excellent photostability, and exhibits good resistance to interference from ions, amino acids, and viscosity. Furthermore, this dye demonstrates superior fluorescence performance in a variety of common solvents, with fluorescence quantum yields exceeding 0.70. Experimental results show that this fluorescent dye can precisely target lysosomes in living cells, demonstrating promising applications in the field of bioimaging.

The application discloses a kind of strong electron donor triphenylamine modified coumarin dyes, its synthesis method and application;The dye has blue-green light excitation characteristics, the maximum absorption wavelength is 415-425 nm, the maximum emission wavelength is 495-505 nm, and excellent lysosome targeting and positioning ability is shown.It overcomes the problem of low efficiency of traditional coumarin as photosensitizer in molecular structure design, realizes the efficient I type photodynamic effect, can generate active oxygen under light efficiently.In addition, this dye has good cell membrane permeability and low dark toxicity, suitable for biomedical imaging, photodynamic therapy of tumor and other fields.The synthesis method is simple, raw materials are easy to obtain, and the yield is high, suitable for large-scale production.Experiments show that the dye can effectively enrich in cell lysosomes, realize precise killing of cancer cells, and show great potential in cancer diagnosis and treatment integration.

Provided herein are antigen-binding proteins (ABPs) that selectively bind to M6PR and its isoforms and homologs, and compositions comprising the ABPs. Also provided herein are bispecific antigen-binding proteins (ABPs) that selectively bind to internalizing receptors, and a soluble target molecule or cell surface target molecule and its isoforms and homologs, and compositions comprising the ABPs.

The application discloses a kind of targeting lysosome polypeptide, lysosome fluorescent probe and kit, belong to the field of biotechnology.The targeting lysosome polypeptide sequentially includes A, B, C, D four parts from N-terminal to C-terminal, wherein, A part is cell penetrating peptide sequence, B part is lysosome targeting positioning sequence, C part is connecting peptide sequence, D part is fluorescent protein sequence.The polypeptide can quickly enter cell and target positioning in lysosome, has good biological safety and stability, can be applied as lysosome fluorescent probe, is suitable for the fluorescence imaging of lysosome in different living cells, and has specificity for lysosome staining.And lysosome polypeptide probe kit can be developed therefrom, to provide accurate lysosome organelle positioning and convenient application for scientific experimental research.

Provided herein are compositions, systems, kits, and methods for treating nervous system injuries caused by trauma or neurodegeneration or aging in a subject by administering a CSPG or SOCS3 reduction peptide (CRP and SRP respectively), or a nucleic acid sequence encoding the CRP or SRP, wherein both the CRP and SRP comprise a cell membrane penetrating domain, and a lysosome targeting domain, and the CRP further comprises a chondroitin sulfate proteoglycan (CSPG) binding domain, and the SRP further comprises a suppressor of cytokine signaling-3 (SOCS3) binding domain.

The application discloses a kind of lysosome-targeting protein modulators based on upconversion nanomaterial-DNA nanostructure and preparation method thereof.The lysosome-targeting protein modulators are combined by covalent bond from carboxyl functionalized upconversion nanoparticles and amino-modified DNA nanostructure, mainly enter cancer cells through folate receptor, after near infrared light illumination and glutathione response, the target protein combined is transported into lysosome and degraded.The lysosome-targeting protein modulators of the application have the advantages of light affinity, high controllability and storage stability, are easy to be metabolized by organism, and have good application prospect in the field of cell biology and cancer targeted therapy.

The present invention provides a glucose transporter (GLUT)-based lysosome targeting chimera. The lysosome targeting chimera can effectively enrich and degrade in lysosomes different types of target proteins on the cell surface and outside the cell. The present invention further provides an application of the lysosome targeting chimera, and an antibody-drug conjugate obtained by conjugating the lysosome targeting chimera with a cytotoxic drug.

The invention discloses a polypeptide targeting lysosome, a lysosome fluorescent probe and a kit, and belongs to the technical field of biology. The polypeptide of the targeted lysosome sequentially comprises a part A, a part B, a part C and a part D from the N end to the C end, the part A is a cell penetrating peptide sequence, the part B is a lysosome targeted positioning sequence, the part C is a connecting peptide sequence, and the part D is a fluorescent protein sequence. The polypeptide can rapidly enter cells and target and locate in lysosome, has good biological safety and stability, can be used as a lysosome fluorescent probe, is suitable for fluorescence imaging of lysosome in different living cells, and has specificity for lysosome staining. Therefore, a lysosome polypeptide probe kit can be developed, and accurate lysosome cell device positioning and convenient application are provided for scientific experimental research.

The application discloses a dual-response fluorescent probe and a preparation method and detection application thereof, and belongs to the technical field of fluorescent probes. The probe is prepared by condensation reaction of 4-methyl-7-hydroxy-8-aldehyde coumarin and 4-morpholine aniline, and can simultaneously and specifically respond to peroxynitrite and viscosity. ‑ The probe specifically reacts with ONOO to generate a concentration-dependent fluorescence enhancement, has high selectivity, fast response and good linearity, and the fluorescence is significantly enhanced with the increase of viscosity. The probe has lysosome targeting properties, and can realize real-time imaging and dynamic monitoring of endogenous and exogenous ONOO ‑ in living cells, and presents a high-contrast fluorescent signal in a non-alcoholic fatty liver model mouse liver tissue slice, so that ONOO ‑ overproduction and viscosity increase in a pathological state can be accurately identified.

The application belongs to the field of fluorescent probes, and relates to a lysosome-targeting fluorescent probe and a preparation method and application thereof. An intermediate is prepared by mixing an aldehyde compound, 5-amino fluorescein and 7-bromoheptanoic acid, and then performing a reaction; the intermediate is mixed with morpholine, and then a reaction is performed, so that the lysosome-targeting fluorescent probe is obtained. The application belongs to the construction of a complex molecular system with flexible and modular Ugi four-component reaction, adopts a one-pot method, and is synthesized by a framework template conjugation method, and the yield of the product is between 60% and 80%. The fluorescent probe prepared in the application can target lysosomes, and can be used as a lysosome-targeting imaging agent for living cancer cells. The fluorescent probe containing ferrocene prepared in the application can target lysosomes, and can be used as a lysosome-targeting imaging agent and a therapeutic agent for living cancer cells. The fluorescent probe containing ferrocene prepared in the application can effectively inhibit the growth of Hela and other cancer cells.

The present disclosure provides conjugates comprising a moiety that targets a lysosomal targeting molecule, a linker, and an antibody that specifically binds a cell surface target molecule or extracellular target molecule that is targeted for degradation.

The application belongs to the technical field of biotechnology, and particularly relates to a lysosome-targeting probe and a preparation method and application thereof. The structural formula of the lysosome-targeting probe is shown in formula (I). In formula (I), A is selected from an oxygen atom and a sulfur atom, R1 is selected from a hydrogen atom and an aromatic ring group, R2 is selected from a cyano group and a group shown in formula (II), R3 is selected from an aromatic ring group, and R4 is selected from a hydrogen atom and an alkyl group with a carbon atom number of 1-20. The compound of the application can specifically target lysosomes in tumor cells, emit bright fluorescence, and has a good fluorescence co-localization effect with lysosomes in tumor cells. The compound can be used for lysosome imaging, and the fluorescence intensity thereof is positively correlated with the viscosity of lysosomes in living cells such as tumor cells. The compound can be used for monitoring the viscosity change of lysosomes in living cells under various conditions. The compound can be used as a photosensitizer and a treatment sensitizer, specifically ablates tumors through photodynamic therapy (PDT), restores the sensitivity of tumor cells to radiotherapy and chemotherapy, and enhances the treatment effect of radiotherapy and chemotherapy.

The present application belongs to the technical field of pharmaceutical chemistry, and discloses a lysosome-targeting chimera, which is composed of an azidated mesoporous polydopamine nanoparticle carrier, an alkyne-lysosome-targeting receptor ligand and an alkyne-ALK5 inhibitor. The present application uses the mesoporous polydopamine with high biocompatibility as a carrier, constructs a safe and effective anti-oxidation nano platform, removes reactive oxygen species, reduces the oxidative stress level, and then reduces the secretion of TGF-beta by liver macrophages, simultaneously loads the ALK5 small molecule inhibitor, specifically recognizes and captures ALK5, realizes precise targeting by combining the modified M6P with the high expression CI-M6PR receptor on the surface of HSC, and provides a new technology and idea for clinically treating liver fibrosis.

This invention discloses lysosome-targeting chimeras based on different ratios and molecular weights, their preparation methods, and applications, belonging to the field of biomedical technology. Lysosome-targeting chimera (LYTAC) molecules contain target protein ligands, linkers, and lysosome-targeting receptor ligands. The core of this invention lies in systematically regulating the molecular weight ratio (range 1:1 to 1:10) between the target protein ligand and the lysosome-targeting receptor ligand, as well as the total molecular weight of LYTAC (range 1000 Da to 5000 Da), to obtain a series of LYTAC molecules with different properties. This invention provides a method for preparing the LYTAC molecules via chemical coupling. Experiments show that by optimizing the above parameters, the LYTAC molecules prepared by this invention can significantly improve the degradation efficiency and specificity of extracellular and membrane-associated target proteins (such as PD-L1, EGFR, etc.), while optimizing their pharmacokinetic properties, showing broad application prospects in the treatment of cancer, neurodegenerative diseases, and other fields.

The present application relates to the technical field of biotechnology, and particularly relates to a lysosome-targeted calcium ion fluorescent probe and application thereof. The calcium ion fluorescent probe provided by the present application has high sensitivity fluorescent response to calcium ions, and is not interfered by pH, and can be used for monitoring dynamic changes of lysosome calcium ions. Meanwhile, the lysosome calcium ion fluorescent probe in the present application has good biocompatibility, low background fluorescent interference and other advantages, makes up for the deficiency of traditional commercialized calcium ion fluorescent probes, and has wide application prospect in the field of acute liver injury and other liver diseases in vivo.

The invention discloses a lysosomal targeted photosensitizer based on a BODIPY structure as well as a preparation method and application of the lysosomal targeted photosensitizer. The lysosome targeting photosensitizer is a photosensitizer for photodynamic therapy, has obvious lysosome targeting ability, can be effectively enriched in a lysosome, and can generate strong damage ability to the lysosome after illumination. The invention also provides an application of the lysosomal targeted photosensitizer in preparation of drugs for treating tumors, and in-vivo activity evaluation of the photosensitizer proves that the pH responsive group in the structure of the photosensitizer may have certain help in improvement of tumor tissue targeting ability of the photosensitizer. The target photosensitizer-mediated PDT induces tumor cell apoptosis by bidirectionally regulating an autophagy pathway, so that the anti-proliferative activity is exerted, and the significantly improved anti-tumor efficacy is shown.

The application provides a kind of lysosome-targeted iridium complex and its preparation method and application.Iridium complex cation and coordination anion comprising the structure shown in formula I or formula II.The metal iridium complex prepared by the application has novel structure, lysosome targeting property and phosphorescence property, can not only realize phosphorescence imaging of cell and tissue, but also can be used as photosensitizer to produce reactive oxygen under light, for photodynamic therapy of tumor.In weak acid condition, the phosphorescence of the complex is significantly enhanced, and the ability to produce singlet oxygen and catalyze NADH is also increased, so it has more effective killing ability to lysosome and tumor.The preparation method of the application has the advantages of simple preparation process, high yield and good repeatability.The metal iridium complex prepared by the application can be used for biological imaging and photodynamic therapy of tumor.

The invention provides a switch element capable of realizing specific response and a lysosomal targeting chimera containing the response switch, which are verified to be capable of specifically degrading target protein contained in tumor cells only in a tumor microenvironment without influencing functions of normal cells of an organism, are simple and convenient in preparation steps, can be used for preparing immune checkpoint blocking drugs, and can be used for preparing immune checkpoint blocking drugs. The tumor treatment effect is improved, the transformation problem and the problem of tumor toxicity in target removal in the prior art are solved, and efficient and safe anti-tumor immunotherapy can be achieved.

The application belongs to the technical field of biotechnology, and particularly relates to a kind of multivalent lysosome targeting antibody platform based on DNA tetrahedron.The application constructs a kind of lysosome targeting chimera based on DNA tetrahedron, uses general-purpose secondary antibody as general-purpose binding site, is connected with commercial primary antibody, solves two major core defects of lack of aptamer resources in the prior art and the need to redesign DNA assembly sequence for new target, realizes the efficient degradation of different target proteins "plug and play";The chimera can still maintain structural integrity in complex physiological environment, and after connecting the commercial primary antibody, the target protein can be mediated by the lysosome pathway to realize non-consumption and continuous degradation, which greatly reduces the research and development cost and cycle of targeted protein degradation drugs, significantly improves the application flexibility and degradation efficiency, and is especially suitable for the preparation of antitumor drugs.

This invention discloses a highly efficient oligonucleotide drug delivery system based on a fusion peptide, its preparation method, and its applications. The system includes a fusion peptide and an oligonucleotide drug. The fusion peptide is formed by linking a targeting peptide with a sorting signal peptide of a lysosomal targeting receptor on the cell surface. The fusion peptide is linked to the oligonucleotide drug via a linker. The advantages of this invention include: targeted, efficient, and stable delivery of oligonucleotides into cells to achieve gene therapy effects; low immunogenicity; high safety; high delivery efficiency; and wide applicability.

The invention relates to the technical field of biological medicine, in particular to a lysosome targeting chimeric molecule based on IGF2R-D11 structural domain targeting polypeptide and application of the lysosome targeting chimeric molecule. A novel polypeptide capable of being specifically combined with an insulin-like growth factor 2 receptor is obtained by screening through a phage display technology, the polypeptide is used as a key component and is fused with a targeting antibody through a genetic engineering method, and a bifunctional chimeric molecule capable of efficiently internalizing and mediating target protein targeting lysosome is constructed. A new technical platform is provided for the field of targeted protein degradation, and the method has important application value in the fields of tumor immunotherapy, autoimmune diseases and the like.

The invention discloses an application of a compound Hispidol or a pharmaceutically acceptable salt thereof in preparation of a lipophagy activator. The invention discovers and verifies for the first time that Hispidol can target lysosome, promote liver cell lipophagy and accelerate removal of lipid droplets in liver cells so as to relieve fatty degeneration. In a mouse MASH model, the Hispidol can also significantly promote lipophagy and relieve MASH. The invention relates to a novel application of a lysosome targeting mechanism of Hispidol in enhancing lipophagy activity of liver cells so as to remove lipid droplets and improve the pathological process of liver lipid accumulation and metabolic dysfunction related steatohepatitis (MASH).

The invention belongs to the technical field of biological medicines, and provides a sound-sensitive agent and lysosome targeted degradation polypeptide coupled drug-loaded nano preparation as well as a preparation method and application of the sound-sensitive agent and lysosome targeted degradation polypeptide coupled drug-loaded nano preparation. In the invention, the sonosensitizer contains an N-oxide structure, and energy circulation is changed due to intramolecular movement limitation during aggregation of molecules, so that enhanced fluorescence and ROS are generated, and the sonosensitizer is more suitable for sonodynamic therapy. The sonosensitizer can generate a large amount of active oxygen under the stimulation of ultrasonic waves, ROS is generated through targeted mitochondria, tumor ICD is efficiently activated, and the sonosensitizer is used for achieving PCa sound-immunotherapy.

The invention discloses a lysosome targeting fluorescent probe compound based on a hydrogen peroxide response group protection mechanism. The lysosome targeting fluorescent probe compound comprises a naphthalimide fluorophore, a morpholine group and an N-methyl iminodiacetic acid borate (MIDA borate) protection structure. The morpholine group endows the lysosome with targeting ability, the MIDA borate improves the blood circulation stability, and the naphthalimide fluorophore generates a fluorescence signal after responding to H2O2. The synthesis method comprises the steps of synthesis of a naphthalimide precursor, introduction of a morpholine group and protection of MIDA borate. The probe can specifically recognize H2O2, the lowest detection limit reaches 0.25 mu M, the probe can target HeLa cell lysosome and realize high-sensitivity detection, and the cytotoxicity is low. Response group protection and targeting functions are creatively combined, the problems that an existing probe is poor in blood circulation stability and insufficient in detection specificity are solved, and the probe has important practical value in the fields of disease mechanism research, early diagnosis, medicine research and development and the like.