552 results about "Targeting ligands" patented technology

In accordance with at least one aspect of this disclosure, there is provided an imaging agent, a including dye compound conjugated to an antigen specific targeting vector which can be particularly advantageous because their behavior in vivo can contribute to superior optical imaging properties, for example, by significantly increasing the target-to-background ratio of imaged tissues, leading to higher resolution imaging, and ultimately providing for better recognition of malignant tissue for resection and margin assessment and improved visualization during minimal invasive laparoscopic surgery, for example. A method of imaging tumor cells in a subject, can include, administering an imaging effective amount of an imaging agent according at least one embodiment of the invention; 2-4 hours after administration of the imaging agent, irradiating a region in the subject in which tumor cells are expected to be found with at a wavelength absorbed by the imaging agent; and detecting a signal from the imaging agent, thereby imaging the tumor cells, wherein the target-to-background ratio 2-4 hours after administration is from about 2.75 to about 15.

The invention is based, at least in part, on the discovery that replacement of a key bond in the near-infrared fluorophore with a carbon-carbon bond conjugation to a targeting ligand results in vastly increased stability as compared to NIR fluorophores without such a bond, while preserving ligand and zwitterionic properties. In at least one aspect, the invention provides an imaging agent dye comprising a charge-balanced imaging agent conjugated to a targeting vector, wherein the targeting vector is a PSMA binding vector, such as dPSMA-617 or KUE, a FAP binding vector, a bombesin receptor binding vector, or a somatostatin receptor binding vector, and the charge-balanced imaging agent is ZW-800-1, ZW-830-1, or ZW-700-1-Forte.

The invention belongs to the technical field of biological medicine, and discloses an engineering bionic exosome with an anti-aging effect and a preparation method and application thereof, and the preparation method comprises the following steps: (S1) preparing a bionic cell membrane modified targeting ligand: adding collagen, mitochondrial targeting polypeptide, a condensing agent and 4-dimethylaminopyridine into an organic solvent, and stirring to obtain the bionic cell membrane modified targeting ligand; activating under a protective atmosphere, and then adding lysine into the system to react, so as to obtain a bionic cell membrane modified targeting ligand; and (S2) embedding the bionic cell membrane modified targeting ligand into the engineered exosome bionic membrane, and entrapping an active substance to form the engineered bionic exosome. The exosome provided by the invention has better skin permeability, mitochondrial targeting effect and cell endocytosis effect, has better protection effect on mitochondria, and can realize efficient delivery of active substances.

The invention relates to a bionic exosome for anti-inflammation and repair as well as a preparation method and application thereof, and belongs to the field of cosmetics. The bionic exosome provided by the invention comprises a membrane structure and an internal load phase, the membrane structure comprises a phospholipid bilayer, a stabilizer and a targeting ligand; the internal load phase comprises a solvent and an active component; the phospholipid bilayer is composed of phospholipid compounds; preferably, at least one of the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 and the 1, 2-dioleoyl-sn-glycerol-3-phosphoethanolamine is adopted as the phospholipid compound, and at least one of the distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 and the 1, 2-dioleoyl-sn-glycerol-3-phosphoethanolamine is adopted as the phospholipid compound; at least one of cholesterol, phytosphingosine and sodium stearoyl glutamate is preferably adopted as a stabilizer, so that the stabilizer of the obtained bionic exosome is improved, and the bionic exosome has the advantages of high encapsulation efficiency, good encapsulation efficiency stability, simplicity in operation, excellent anti-inflammatory and repairing effects and the like.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents such as siRNAs, able to Inhibin Subunit Beta E (INHBE) gene expression. Also disclosed are pharmaceutical compositions that include INHBE RNAi agents and methods of use thereof. The INHBE RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the INHBE RNAi agents in vivo provides for inhibition of INHBE gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by INHBE gene expression, such as obesity, diabetes, liver inflammation, dyslipidemia, or metabolic disease.

The present disclosure relates to compounds, compositions and methods for treating diseases or conditions mediated by aberrant histone deacetylase 8 (HDAC8) activity. In some embodiments, the disclosed compounds comprise an HDAC8 targeting ligand TL moiety covalently linked to a degradation determinant moiety that recruits E3 ubiquitin ligase to HDAC8. In some embodiments, the degradation determinant can bind to an E3 ligase, which is a von Hippel-Lindau (VHL) tumor suppressor, and the E3 ligase can bind to an E3 ligase, which is a Von Hippel-Lindau (VHL) tumor suppressor.

The invention discloses a nanometer delivery device for a gastric cancer targeted drug and a use method of the nanometer delivery device, and belongs to the technical field of drug targeted delivery. The device comprises a molecular recognition and optimization module which is responsible for accurately recognizing a tumor cell specific molecular marker and providing personalized treatment strategy recommendation; the nano-carrier design module is used for designing multifunctional lipid-polymer hybrid nano-particles and carrying out surface targeting ligand modification; the intelligent drug loading module is used for improving the stability and controllability of drug loading based on a pH / temperature sensitive release mechanism and effectively reducing the toxic influence of non-targeted tissues; the molecular imaging and monitoring module integrates a nanoprobe imaging technology and a quantum dot tracing technology, constructs a treatment-imaging integrated system, realizes real-time dynamic monitoring of a treatment process, and provides instant feedback of a molecular level; and the risk assessment module is used for establishing a safety database and providing dynamic risk assessment of the treatment process through a biological safety assessment system and long-term tracking management.

This invention provides Degrons and Degraders that covalently bind to cereblon which is a component of the E3 ubiquitin ligase. The Degrons provided herein can be used to modulate the activity of cereblon either alone or as covalently linked to a Tail. In addition, the Degron can be linked to a Targeting Ligand which binds to a Target Protein to provide a Degrader.

The invention discloses a preparation method of a targeting system based on bio-orthogonal chemistry, the targeting system comprises gel GelMA-DBCO modified with a targeting receptor DBCO and nanoparticles NV-N3 modified with a targeting ligand azide group, the preparation method comprises the following steps: respectively dissolving GelMA and DBCO-NHS, mixing, adding triethylamine, and stirring at room temperature for reaction to obtain GelMA-DBCO; the preparation method comprises the following steps: adding GelMA-DBCO into a solution containing a photoinitiator, and carrying out ultraviolet crosslinking to obtain GelMA-DBCO gel; the preparation method comprises the following steps: adding Ac4ManNAz into a culture medium of MSC to obtain mesenchymal stem cells MSC with N3 modified on the surface, digesting and collecting cells, and extruding the MSC by using a liposome extruder to pass through a filter membrane to obtain nano-particles with azido modified on the surface; and purifying by centrifuging, and resuspending to obtain the NV-N3. The invention also provides application of the targeting system in preparation of products for treating spinal cord injury. The targeting system provided by the invention has strong specificity and stability, good biocompatibility and biodegradability, and effectively improves the targeting ability of the nanoparticles in a spinal cord injury area.

The present disclosure is a polyethylene glycol modified zwitterionic fluorescent probe. The core luminescent group of the fluorescent probe of the present disclosure is a heptamethine chain which is connected by a phenoxy bridge and has a rigid ring structure in the center. The two ends of the heptamethine chain are two sulfonic indole groups, and two polyethylene glycol chains are connected with the indole groups. A tumor targeting ligand is connected with a luminescent group through one polyethylene glycol chain and one alkaline amino acid spacer. The probe of the present disclosure can be connected with polypeptides, small molecules and antibodies having a tumor targeting function, thereby achieving near-infrared fluorescence imaging for tumor targeting. The probe of the present disclosure has good druggability, and is extremely suitable for industrial production and clinical promotion.

The invention relates to the technical field of biological medicine, in particular to a functionalized targeted liposome and application thereof, and the functionalized targeted liposome comprises lipid and a targeted ligand, wherein the targeting ligand can be specifically combined with a TREM2 receptor. According to the lipidosome, the targeting ligand can be specifically combined with the TREM2 receptor, accurate targeting of cells with the surface containing the TREM2 receptor is achieved, it is ensured that the cells directly act on target cells, the accuracy of a delivered substance is further improved, and the lipidosome has the advantages of being targeting, high in stability, small in side effect and high in bioavailability. The functionalized targeted liposome can be applied to the development of drug carriers, pharmaceutical compositions and the like, and has wide application prospects, for example, the liposome is dynamically connected with hydrogel molecules through a borate bond to prepare a hydrogel pharmaceutical composition containing the functionalized targeted liposome, and the application prospect is wide. The liposome disclosed by the invention can respond to an inflammatory environment according to pH and ROS changes of a surrounding environment to release the liposome disclosed by the invention, targets cells with TREM2 receptors on the surfaces, namely microglial cells (with the TREM2 receptors on the surfaces) by virtue of the target ligands exposed on the surfaces, regulates the polarization state of the cells, inhibits the polarization of the cells to a pro-inflammatory M1 type and promotes the polarization of the cells to an anti-inflammatory M2 type, so that the anti-inflammatory effect of the liposome is improved. Therefore, the local microenvironment of the spinal cord injury part is improved, and nerve regeneration is promoted.

The invention discloses a preparation method of deer spleen aminopeptide powder in the field of bioactive substance extraction and functional material compositing, and the performance of the deer spleen aminopeptide powder is improved by compositing a multi-stage functional modified material and deer spleen aminopeptide. The preparation method comprises the following steps: cleaning, homogenizing and crushing fresh deer spleen, extracting with a phosphate buffer solution, adjusting the pH value, carrying out enzymolysis, inactivating enzyme, and treating with an ultrafiltration membrane and a nanofiltration membrane in a specific molecular weight range to obtain a concentrated solution; and mixing the concentrated solution with a multi-stage functional modified material under proper conditions, sterilizing, pre-freezing, and freeze-drying to obtain the deer spleen aminopeptide powder. Wherein the modified material is constructed through quaternization modification, nanopore loading, enzyme inhibitor coupling and targeting ligand modification, and has the functions of charge repulsion, steric hindrance, enzyme inhibition and targeting recognition. The deer spleen aminopeptide powder prepared by the invention has high stability and good bioavailability, and is suitable for functional food or health care products.

A drug delivery platform providing flexible fine tune of cell therapy is disclosed herein. Particularly, an engineered fusion protein is coupled with a high affinity ligand carrying at least one payload of drug to be internalized by the transplanted cell to observe or regulate transplanted cell therapy effects.

The invention discloses a frontalon tooth healing targeting nano preparation and a preparation process thereof, belongs to the technical field of nano medicines, and aims to solve the problems that the natural regeneration capacity of teeth is limited and the combination of ethnic drugs and modern biotechnology is caused due to the lack of a targeting inhibition means for USAG-1. Comprising an anti-USAG-1 monoclonal antibody, ethnic drug components and a nano-carrier, the anti-USAG-1 monoclonal antibody is connected to the surface of the nano-carrier through covalent bonds, the ethnic drug components are loaded in the nano-carrier through physical action, and the nano-carrier is a polylactic acid-glycolic acid copolymer or chitosan; the anti-USAG-1 monoclonal antibody is used as a targeting ligand, is high in targeting property, can accurately reach a tooth focus, improves the drug utilization rate, enhances the curative effect, integrates multiple ethnic drug components, exerts a synergistic effect, can increase the contact area between the ethnic drug components and a biological membrane, promotes the absorption and transport of the drug, and improves the bioavailability of the drug. And the medicine can better play a treatment role.

The present invention provides a conjugate comprising: (a) a CNS targeting ligand, (b) a hydrophilic polymer of polyethylene glycol (PEG), polylactic acid (PLA), polylactic acid-co-glycolic acid (PLGA), or glucan, and (c) a flavonoid. The present invention also provides a micelle nanoparticle composition comprising: (a) an outer shell comprising the conjugate, optionally (b) an inner shell comprising oligomeric (-)-epigallocatechin gallate (OEGCG), and optionally (c) a CNS disease treatment molecule encapsulated in the inner shell. The invention also provides a method of treating a CNS disease by administering to a subject an effective amount of a nanoparticle composition of the invention. The CNS targeting ligand targets a CNS tissue and delivers an active ingredient to the CNS tissue for treating a CNS pathological condition.

The invention relates to the technical field of biological medicine, in particular to a composite drug-loaded nano preparation and a preparation method thereof. The composite drug-loaded nano-preparation comprises a drug-loaded nano-liposome, and a biological enzyme and a myofibroblast targeting ligand which are loaded on the surface of the drug-loaded nano-liposome, the drug-loaded nano-liposome is a nano-liposome in which an anti-fibrosis drug is encapsulated; the mass ratio of the drug-loaded nano-liposome to the biological enzyme to the myofibroblast targeting ligand is (6-15): (0.5-4): (0-3). According to the invention, a composite drug-loaded nano preparation for pulmonary drug delivery in an aerosol inhalation manner is constructed, and the myofibroblast targeting ligand and the biological enzyme are jointly modified on the surface of the drug-loaded nano liposome; and the composite nano preparation (CLG-CS-FAP-NIN) which has myofibroblast targeting and can degrade excessive collagen in an extracellular matrix is prepared and is used for treating the pulmonary fibrosis.

Keto-amide based FAP-targeted ligands, conjugate comprising same, pharmaceutical compositions comprising same, and methods of use for imaging and treatment.

The invention discloses a multi-technology combined medication analysis platform of an oligonucleotide drug, which relates to the technical field of drug analysis and is technically characterized by comprising an oligonucleotide drug delivery technology module, a liposome, a polymer nanoparticle or an exosome is selected as a delivery carrier, the surface of the delivery carrier is modified with hydrophilic polyethylene glycol or a targeting ligand, and the oligonucleotide drug delivery technology module is connected with the oligonucleotide drug delivery module. The performance of the material is represented by dynamic light scattering and a transmission electron microscope; the multi-technology platform analysis module integrates RT-qPCR, LC-FL, LC-MS / MS and LC-HRMS technologies, is respectively used for target gene expression quantification, drug distribution tracking, drug principal component quantification and metabolite structure analysis, establishes a cross validation rule, and requires a correlation coefficient R2gt of an LC-MS / MS quantitative result and RT-qPCR expression data; 0.95%, 0.95%; the pharmacokinetic evaluation module constructs a PBPK model to predict human pharmacokinetic parameters, and draws a drug metabolism network diagram in combination with an LC-HRMS metabolite identification result; by integrating various advanced analysis technologies, the problems of low sensitivity, poor specificity and difficult metabolite analysis in the prior art are solved.

The invention lies in the field of treatment and prophylaxis of muscle wasting disorders, in particular the ones involving a genetic factor that can be targeted by a delivery of a therapeutic nucleic acid into the muscle cells. In line with the latter aspect, disclosed herein are pharmaceutical compositions and advantageous components thereof that substantially enhance the effective delivery and release of a therapeutic nucleic acid into the right internal compartment of the muscle cell, such as the cytosol and / or the nucleus, in which compartment it can reach and act upon its genetic target. As disclosed herein, this substantially enhanced delivery and release is achieved by a provision of an endosomal-escape-enhancing saponin in the disclosed herein pharmaceutical compositions comprising therapeutic nucleic acids and, optionally, muscle cell-targeting ligands conjugated therewith. As for the first time demonstrated herein, these saponin types not only surprisingly retain their endosomal-escape-enhancing properties in fully differentiated muscle cells but also can in an unconjugated state successfully be delivered thereto together with the therapeutic nucleic acids.

The invention provides sonodynamic targeted drug-loaded nanoparticles as well as a preparation method and application thereof, and belongs to the field of targeted drug delivery preparations. The sonodynamic targeting drug-loading nanoparticle provided by the invention comprises a porous carrier, a drug loaded in the porous carrier and a targeting ligand chemically modified on the outer surface of the porous carrier, the porous carrier is a hydrogen bond organic framework; a construction unit of the hydrogen bond organic framework is a metalloporphyrin complex. After the sonodynamic targeting drug-loading nano-particle provided by the invention is injected into a 4T1 tumor-bearing BALB / c mouse body for 6 hours, fluorescence of the sonodynamic targeting drug-loading nano-particle is observed on a tumor, and a signal is continuously enhanced; after 14 days of administration, the tumor growth is obviously inhibited, and good targeting and anti-tumor effects are achieved.

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.

The invention provides a nano-drug carrier and a drug release system, the nano-drug carrier comprises a drug loading core and a responsive shell arranged outside the drug loading core, and the drug loading core is loaded with a nano-drug; the surface of the responsive shell is modified with a targeting ligand, and the targeting ligand can specifically target pain-related cells or tissues. According to the nano-drug carrier and the drug release system provided by the invention, precise long-acting treatment of chronic pain is realized through combination of an environment-responsive carrier and an active targeting technology. The technology can significantly improve local accumulation of the medicine and reduce systemic toxicity, and is suitable for management of intractable pains such as neuropathic pains and osteoarthritis.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents such as siRNAs, able to Inhibin Subunit Beta E (INHBE) gene expression. Also disclosed are pharmaceutical compositions that include INHBE RNAi agents and methods of use thereof. The INHBE RNAi agents disclosed herein may be conjugated to targeting ligands to facilitate the delivery to cells, including to hepatocytes. Delivery of the INHBE RNAi agents in vivo provides for inhibition of INHBE gene expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by INHBE gene expression, such as obesity, diabetes, liver inflammation, dyslipidemia, or metabolic disease.

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

Conjugates comprising a fibroblast activation protein α (FAP-α)-targeted ligand, a bifunctional or trifunctional linker, and a phosphatidylinositol-3-kinase (PI3k) inhibitor; uses of the conjugates in the manufacture of a medicament for inhibiting progression of fibrosis in a subject; and a method of use in inhibiting progression of fibrosis in a subject.

The invention discloses a radionuclide coupling medicine and a medicine composition and application thereof. Specifically, the precursor of the radionuclide coupled drug has a structure as shown in a formula I, and LG represents a targeting ligand; s represents a spacer; l represents a linker; and C represents a chelating agent capable of containing a radionuclide. The radionuclide-conjugated drug may specifically deliver a radionuclide to a target cell. When the coupling drug contains one LG, the coupling drug can specifically deliver the radionuclide to a target cell; when the coupling medicine contains two LGs, the coupling medicine can play a role in various ways, so that the treatment effect is improved, and the toxic and side effects are reduced; meanwhile, due to the existence of the two LGs, the affinity of the coupling medicine to target cells is also enhanced, and the off-target toxicity is reduced. # imgabs0 #

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents such as small interfering RNA (siRNA) molecules, able to inhibit proprotein convertase subtilisin kexin 9 (PCSK9) gene expression. Also disclosed are pharmaceutical compositions that include PCSK9 RNAi agents and methods of use thereof. The PCSK9 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the delivery to hepatocyte cells. Delivery of the PCSK9 RNAi agents in vivo provides for in vivo provides for inhibition of PCSK9 gene expression and thereby reduction of PCSK9 protein. The RNAi agents can be used in methods of treatment of diseases or disorders mediated at least in part by PCSK9 gene expression, including among others hypercholesterolemia, familial hypercholesterolemia including heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), familial hypobetalipoproteinemia, hyperlipidemia, coronary artery disease, polygenic dyslipidemia, heart disease, cardiovascular disease (CVD) including clinical atherosclerotic cardiovascular disease (ASCVD).

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 invention relates to the technical field of cardiovascular diseases, in particular to a method for verifying an in-vivo targeted delivery function of a reagent based on an atherosclerosis model. The method comprises the following steps: acquiring lesion characteristic data of an atherosclerosis site, wherein lesion characteristics comprise a lesion position, endothelial permeability, an inflammation state and a vulnerability index; preparing targeted nano microbubbles according to the lesion characteristic data, intravenously injecting the targeted nano microbubbles into a preset atherosclerosis model body, and performing multi-modal image tracking analysis to obtain in-vivo circulation distribution data of the microbubbles. Targeted nano microbubbles are customized and designed based on plaque feature data, the targeting specificity of inflammatory components such as macrophages is remarkably improved by utilizing a double-targeting ligand modification technology, and the problem of low recognition efficiency of a traditional single targeting system is solved.

Methods for treating Alzheimer's disease and other neurodegenerative disorders in which the capacity of microglia and / or astrocytes has been altered and impaired are described. The method comprises the step of carrying out brain targeting on PD-L1 by using a brain targeting nanogel which is loaded with a PDL1 antibody and is functionalized by two specific targeting ligands. The nanogel can successfully cross the blood brain barrier to release the antibody, reduce the expression of PD-L1 in the brain, and maintain the integrity of BBB at the same time.