233 results about "Targeting ligands" patented technology

The invention relates to the technical field of compound preparation and medicine, in particular to a boron atom-labeled compound for targeting fibroblast activating protein as well as a preparation method and application of the boron atom-labeled compound. The preparation method comprises the following steps: carrying out acid amine condensation on (4-(((2, 5-dioxopyrrolidine-1-yl) oxy) carbonyl) phenyl) boric acid and an FAP targeting ligand to obtain a boron atom-labeled compound targeting the fibroblast activating protein; and the FAP targeting ligand is FAPI-46 or FAP-2286 (Fibroblast Amplified Polymorphism). The compound is easy to prepare, high in purity and good in stability, the content of boron atoms in tumor tissue can be greatly increased, and a treatment basis is provided for boron neutron capture therapy.

Lipid nanoparticle compositions for the delivery of nucleic acids are provided.SOLUTION: In various embodiments, the lipid nanoparticle comprises an ionizable lipid of Formula (I). Also provided are methods of using such lipid nanoparticle compositions to achieve targeted delivery of therapeutic cargo without the need for a targeting ligand.SELECTED DRAWING: None

The invention belongs to the field of biomedical materials, and discloses a preparation method and application of a mesoporous polydopamine nano preparation loaded with ultra-small nano enzyme. The nano preparation takes mesoporous polydopamine nanoparticles as a carrier skeleton and is combined with ultra-small nano enzyme through an in-situ reaction: the mesoporous polydopamine nanoparticles can efficiently carry drugs and accurately deliver the drugs to inflammatory tissues such as psoriasis, gout, colitis and the like by virtue of a modified targeting ligand by virtue of high specific surface area, biocompatibility and modifiability; the ultra-small nano enzyme has catalytic activity of catalase and the like, and can remove active oxygen and relieve oxidative stress. The two components are combined to achieve a synergistic effect, so that the catalytic efficiency of the enzyme is improved by virtue of the characteristics of the carrier, the high activity of the enzyme under different conditions is maintained by virtue of the stability of the carrier, and the platform can synchronously realize targeted delivery, enzymatic treatment and drug controlled release, and has a wide application prospect in the fields of inflammatory disease intervention and wound repair. And an efficient, accurate and low-toxicity universal treatment strategy is provided for chronic inflammatory diseases.

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.

The invention relates to the technical field of biomedicine nanotechnology, in particular to a high-stability engineered exosome based on rigid hydrophobic anchoring and micelle disassembly and purification as well as a preparation method and application of the high-stability engineered exosome. According to the invention, a ternary surface structure of rigid hydrophobic anchoring-hydrophilic polymer spacer arm-targeting ligand (L-S-T) is constructed, cholesterol hemisuccinate or multi-branched lipid is selected as an anchoring group, and the problem that conventional phospholipid modification is easy to fall off in vivo and in an albumin-containing preparation is obviously solved; a technology of'micellar insertion after temperature control 'combined with'CMC critical concentration adjustment and purification' is adopted, lossless insertion of functional molecules is realized by utilizing thermodynamic driving force, and residual micelles are induced to be disintegrated into monomers by adjusting the concentration of a system to be lower than the concentration of critical micelles, so that efficient removal of free impurities is realized through conventional ultrafiltration. The engineered exosome has the advantages of long circulation, high targeting and excellent storage stability, and has important clinical application and commercial transformation prospects.

The invention belongs to the field of biosensing and microbiological detection, and relates to a staphylococcus aureus rapid counting method based on fluorescence confinement discretization. According to the method, oat bran is used as a natural carbon source, lysozyme active fragments are used as targeting ligands, targeting carbon quantum dots are synthesized through a one-step hydrothermal method, the targeting carbon quantum dots are modified by fluorescent dye SRB to obtain luminescence enhanced carbon quantum dots, and the luminescence enhanced carbon quantum dots can be specifically combined with cell walls of staphylococcus aureus, so that the staphylococcus aureus has stable fluorescence signals. And then, by taking the marked thalli as a core layer and a high-molecular polymer as a shell layer, preparing a core-shell nanofiber membrane by adopting a coaxial electrostatic spinning technology to realize spatial confinement and monomer discretization of the thalli, so that a group fluorescence signal is converted into a single-thalli distinguishable signal, and rapid and sensitive quantitative detection of the staphylococcus aureus is realized. The method is simple, convenient, high in sensitivity, suitable for rapid visualization and quantitative detection of staphylococcus aureus in foods such as dairy products, meat products and beverages, and wide in application prospect.

The invention discloses an esophageal cancer targeting nano-tablet based on a traditional Chinese medicine composition and a preparation method of the esophageal cancer targeting nano-tablet. The targeted nano tablet is prepared from the following refined extracts: a rhizoma paridis total saponin extract, a pseudobulbus cremastrae seu pleiones colchicine derivative extract, a panax notoginseng total saponin extract, a carthamin yellow extract, a thunberg fritillary bulb total alkaloid extract, frankincense-myrrh compound volatile oil, a resin extract and an astragaloside IV extract. The nano-carrier comprises a nano-carrier, a seaweed-laminarin composite extract, a processed rhizoma pinelliae total alkaloid extract and costus root volatile oil, and the costus root volatile oil serves as one of targeting ligands to be used for modifying the nano-carrier. The targeting property is strong: the dual-targeting ligand (costunolide-TOPK affinity peptide) on the surface of the nano-carrier can actively recognize and combine with a specific receptor of esophageal cancer cells, and meanwhile, due to the size (about 100-200 nanometers) of the carrier, the carrier is easy to enrich in tumor tissues through enhanced permeation and retention (EPR) effect, so that the modernization upgrading of the idea of'channel guiding medicine 'is realized.

The application discloses a kind of based on active fragment's targeted ligand generation method, including fragment sequencing process: based on fragmentation method and sequencing method processing ligand molecule for training obtains fragment sequence;Model training process: ligand molecule fragment sequence and target protein amino acid sequence for training are input into targeted ligand molecule generation model, the molecular representation of ligand molecule fragment sequence is extracted by fragment sequence encoder, and the target representation of target protein amino acid sequence is extracted by target encoder, feature fusion is used after fragment sequence decoder output fragment sequence, and optimization model;Targeted ligand molecule generation process: target protein amino acid sequence is input into the model after training, the target representation is extracted by target encoder, and compound information is predicted by priori network and is input into fragment sequence decoder, and output fragment sequence, again based on molecular reconstruction method fragment sequence is recombined into targeted ligand molecule.

The present invention relates to a multi-cluster linker, a preparation method therefor and the use thereof. Specifically, provided is a linker, which is a compound as represented by formula I or a stereoisomer thereof or a pharmaceutically acceptable salt thereof. Further provided is a targeting ligand or targeting ligand delivery conjugate using the linker.

Provided are a pharmaceutical composition and a preparation method therefor. Specifically, provided are an aqueous pharmaceutical composition of a radionuclide-labeled fibroblast activation protein-targeting ligand, and a preparation method therefor. The aqueous pharmaceutical composition has high radiochemical purity.

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 disclosure relates to RNAi agents, e.g., double-stranded RNAi agents, e.g., siRNAs, capable of inhibiting expression of the subunit beta E (INHBE) gene. Also disclosed are pharmaceutical compositions comprising the INHBE RNAi agents, and methods of use thereof. The INHBE RNAi agents disclosed herein can be conjugated to targeting ligands to facilitate delivery to cells, including to hepatocytes. Delivery of the INHBE RNAi agent in vivo results in inhibition of expression of the INHBE gene. RNAi agents may be used in methods of treating diseases, disorders, or conditions mediated in part by the expression of the INHBE gene, such as obesity, diabetes, liver inflammation, dyslipidemia, or metabolic diseases.

The invention discloses an adoptive cell therapy system with tumor targeted activation and acid neutralization characteristics. The system is prepared by adhering a micron-sized layered double-metal hydroxide patch to the surface of an immune cell. The immune cells are any one of macrophages, dendritic cells, T cells and NK cells. The layered double-metal hydroxide patch is adhered to the surface of the immune cell in a manner of co-incubation with the immune cell. Before co-incubation, the layered double-metal hydroxide patch is modified by PEG-COOH in advance and is combined with a specific targeting ligand to form a surface functional layer for realizing efficient selective adhesion of the patch to immune cells and reducing non-specific binding. According to the adoptive cell therapy system, the cell homing effect is utilized, the immune cells carrying the layered double-metal hydroxide patches are enriched at the tumor site, the STING pathway of the immune cells is activated, the anti-tumor effect of the immune cells is promoted, meanwhile, locally free H < + > is consumed, and potent immunotherapy for solid tumors is achieved.

The application belongs to the technical field of biological medicine, and specifically discloses a compound for targeted degradation of fatty acid synthase and application thereof, which has a structure shown in general formula I or a pharmaceutically acceptable salt thereof. The compound provided by the application is designed through a target ligand-connection bridge-E3 ligand structure, realizes efficient degradation, can significantly reduce the level of FASN in high-expression cells, and thus specifically targets cells related to abnormal lipid metabolism. The mechanism of action depends on the ubiquitin-proteasome pathway and is time-dependent. The compound provided by the application has good biological activity of degrading FASN, can be applied to the development of anti-liver cancer drugs, and has a wide application prospect.

The present invention relates to a conjugate comprising a FAP targeting ligand and an effector for use in the treatment and / or diagnosis of endometriosis, as well as associated methods and kits.

This invention belongs to the field of biomedical technology and provides a polypeptide with ATG8 protein binding activity, comprising the following structure: X1-X2-X3-X4-X5-X6-X7; wherein: X1, X2, and X3 are independently selected from glutamic acid or are absent; X4 is selected from tryptophan, phenylalanine, or leucine; X5 is valine; X6 is selected from leucine, isoleucine, or valine; and X7 is selected from valine, tryptophan, phenylalanine, or tyrosine. Compared with existing autophagy inhibitors, this polypeptide has the following superior pharmacokinetic potential and development flexibility in terms of target selection, binding strength, and mechanism of action: the short sequence not only reduces synthesis costs but also leaves more room for modification, which is expected to significantly improve the metabolic stability and drug-likeness potential of the polypeptide; it can serve as a highly efficient ATG8 targeting ligand and can be widely used in the construction of biochemical probes, screening of PPI competitive inhibitors, and the development of targeted delivery systems.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit xanthine dehydrogenase (XDH) gene expression. Also disclosed are pharmaceutical compositions that include XDH RNAi agents and methods of use thereof. The XDH RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the XDH RNAi agents in vivo provides for inhibition of XDH gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by XDH gene expression, such as gout and hyperuricemia.

Embodiments of the invention disclosed herein involve the selective engineering of Sindbis virus so as to generate cells that make enveloped virus-like particles that contain therapeutic mRNAs, and whose membrane proteins have been mutated to serve as modular binding sites for cell-targeting ligands.

The present disclosure relates to oligonucleotides, compositions, and methods useful for reducing GYS2 expression, particularly in hepatocytes. The disclosed oligonucleotides for reducing GYS2 expression can be double-stranded or single-stranded, and can be modified to improve properties such as stronger resistance to nucleases and lower immunogenicity. The disclosed oligonucleotides for reducing GYS2 expression can also include targeting ligands to target specific cells or organs, such as hepatocytes of the liver, and can be useful for treating glycogen storage diseases (e.g., GSDIa, GSDIII, GSDIV, GSDVI, and GSDIX) and related conditions.

The invention relates to a ligand targeting neutrophil and neurons as well as a preparation method and application of the ligand. The ligand for targeting the neutrophil and the neuron is prepared from the following raw materials in parts by weight: 30 to 50 parts of DSPE-PEG-Tet1, 2 to 3 parts of ketal thiol with carboxyl groups at two ends and 30 to 50 parts of a neutrophil targeting ligand, the neutrophil targeting ligand is one or more of sialic acid, an anti-CD66b antibody, an anti-CD177 antibody, an anti-CD16b antibody, N-formylmethionine peptide (fMLF) and an analogue thereof, a CXCR1 / CXCR2 binding peptide, an integrin binding peptide, a selectin ligand and lectin. According to the invention, sequential targeting of neutrophile granulocytes-neurons can be realized, target cells of ischemic lesions can be accurately protected, and the improvement effect on the cerebral infarction area of MCAO rats can be obviously enhanced.

The invention discloses a macrophage-targeting lipid nanoparticle and application thereof in malignant tumor treatment, ID3 mRNA is delivered through the lipid nanoparticle, firstly, an ID3 sequence is subjected to codon optimization to improve the expression efficiency and stability of ID3 protein, and the core treatment effect is enhanced; the lipid composition and the targeting ligand of the nanoparticles are further optimized, and mannose modified PEG lipid material (DSPE-PEG2000-Mannose) is specifically combined with the CD206 receptor on the surface of the macrophage, so that the targeting property and the transfection efficiency of the delivery system are remarkably improved. The ID3 mRNA is delivered to the macrophages by utilizing the lipid nanoparticles of the targeted macrophages, so that the tumor cells can be effectively swallowed and killed, the in-situ treatment of pancreatic cancer is realized, and better tumor inhibition and immune activation effects are achieved.

The present application provides a PSMA-targeting ligand compound and chelate thereof and use thereof. The structure of the PSMA-targeting ligand compound is shown in formula I, wherein R1, R2 and R4 are each independently selected from H and optionally substituted C1-C5 linear or branched alkyl; R3 is selected from optionally substituted aryl ring group and optionally substituted aromatic heterocyclic group; X is a sulfur or oxygen atom; Y is selected from a chemical bond and -NH-(CH2)m-, wherein m is an integer selected from 0-18; and Z is a radioactive metal ion chelating group. The pharmacokinetic characteristics of the PSMA-targeting ligand compound are obviously improved, which can be more effectively absorbed by the human body, stably exist in the body, and be taken up and internalized by cancer cells, so that the coupling of the radioactive nuclide can obtain cancer treatment drugs and diagnostic reagents with obviously improved therapeutic effect.

This disclosure relates to RNAi agents capable of inhibiting complement factor B (CFB) gene expression. Pharmaceutical compositions containing CFB RNAi agents and methods of use thereof are also disclosed. The CFB RNAi agents disclosed herein may be conjugated to a targeted ligand containing an N-acetyl-galactosamine ligand to facilitate in vivo delivery to hepatocytes. RNAi agents can be used in methods of treating diseases, disorders, or conditions partially mediated by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membrane proliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), anti-glomerular basement membrane antibody disease (anti-GBM), ischemia-reperfusion injury and T-cell-mediated rejection in kidney transplantation (TCMR), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD) including early and / or intermediate-stage AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated disorders.

The present disclosure relates to compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacetylase 8 (HDAC8) activity. The compounds disclosed comprise HDAC8 Targeting Ligand TL moiety covalently linked to a Dergon moiety recruiting E3 ubiquitin ligase to HDAC8. In some embodiments, the degron may bind the E3 ligase which is von Rippel-Lindau (VHL) tumor suppressor.

The application discloses a kind of nanoclusters with golgi targeting and its preparation method and application, the nanocluster is zinc sulfide nanocluster, the surface of the zinc sulfide nanocluster is coupled with targeting ligand, the targeting ligand can actively target RA synovial activated macrophage, and can target golgi subcellular organelle, the nanocluster can release H2S gas in inflammatory weak acid microenvironment.The application can realize "inflammatory joint enrichment-> macrophage active uptake-> lysosome escape-> golgi deep anchoring" multi-level precise delivery, release H2S gas in inflammatory weak acid microenvironment, fundamentally reshape intracellular Ca 2+ Steady state, relieve endoplasmic reticulum, golgi and mitochondria triple stress, block inflammatory signal pathway, realize the efficient, safe treatment of RA.

The present application belongs to the technical field of biomedicine, and provides a pharmaceutical composition for inhibiting NFKBIZ gene expression, and a use. The present application designs a double-stranded nucleic acid molecule capable of targeting and regulating NFKBIZ gene expression. By means of verifying the gene regulation efficiency of nucleic acid molecules, multiple nucleic acid molecules capable of inhibiting NFKBIZ gene expression are obtained from screening, and efficient inhibition of IκB-ζ protein expression is achieved at the protein level. In addition, the present application verifies a use of a pharmaceutical composition formed by the conjugation of the described nucleic acid molecules and targeting ligand molecules in ophthalmic diseases. The pharmaceutical composition can solve the problems with existing small molecule immunomodulatory drugs of low delivery efficiency and poor therapeutic effect, providing small nucleic acid drugs having tissue-targeted delivery functions, and has the advantages of long duration of efficacy and low side effects. In addition, the pharmaceutical composition has simple ingredients, is easy to synthesize, and has good prospects for translational applications.

The present invention provides a combination of two or more imaging agent conjugates comprising an imaging agent conjugated to a targeting ligand, wherein the imaging agent comprises one or more of: ZW800-1, ZW830-1, ZW700-1-Forte, ZW-DOTA, ZW-PyC3A, ZW-Macropa, ZW-Porphyrin, ZW-NOTA, and ZW-Deferoxamine; and the targeting ligand comprises one or more of: cRGD, dPSMA-617 or KUE, FAP, Bombesin Receptor Binding Vector, or Octreotide Binding Vector, or one or more of the peptides selected from SEQ ID Nos: 1 to 4.

The invention discloses a chondroitin sulfate modified dihydromyricetin solid lipid nanoparticle, and belongs to the field of pharmaceutics. The nanoparticle is composed of a solid lipid component, dihydromyricetin encapsulated in the solid lipid component and a chondroitin sulfate targeting ligand modified on the surface. According to the invention, the chondroitin sulfate is specifically combined with the high-expression CD44 receptor on the surface of the hepatic stellate cell, so that the active targeting delivery of the drug to the hepatic fibrosis focus is realized. The nanoparticles have the characteristics of uniform particle size, high encapsulation efficiency and good slow release effect, can significantly improve the enrichment concentration of dihydromyricetin in the liver, enhance the anti-hepatic fibrosis curative effect and reduce the systemic side effects, and have good application prospects in preparation of hepatic fibrosis targeted therapy drugs.

Provided are a fluorine-18-labeled positron emission tomography (PET) radiotracer for diagnosing neuroinflammation, stroke or cerebral infarction and a method for diagnosing cancer in a subject including administering a fluorine-18-labeled PET radiotracer a subject, obtaining in vivo PET images of the uptake of the fluorine-18-labeled positron emission tomography (PET) radiotracer in a lesion in the subject, and evaluating the uptake of the fluorine-18-labeled radiotracer in the lesion.

Disclosed is a bifunctional compound (degradation agent) comprising a [targeting ligand]-[linker]-[degrader] adduct, the targeting ligand comprising a substituted pyridine compound, the bifunctional compound targeting an epigenetic writing protein desoxyribonucleic acid methyltransferase 1 responsible for maintaining DNA methylation during cell proliferation, for degradation. Also disclosed are pharmaceutical compositions containing the compounds and methods of using the compounds in the treatment of diseases and disorders characterized or mediated by aberrant DNMT1 activity.