449 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 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.

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 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.

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 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.

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 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.

The invention belongs to the field of biological medicine, and relates to a human serum albumin covalent binding type targeted folate receptor micromolecule drug conjugate prodrug and application thereof. The prodrug disclosed by the invention has a structure as shown in a formula I, six-carbon maleimide is used as a site combined with endogenous albumin, and albumin is used as a carrier to deliver the drug. The prodrug can increase accumulation of the drug in tumors under the EPR effect. A dipeptide chain composed of valine and alanine is used as a cleavage site of cathepsin B, an adapter composed of p-aminobenzyl ether and N-methylamino-4-nitrophenol releases drugs in an acidic environment, an azidohexanoic acid structure is added to a side chain of p-aminobenzyl ether, so that the site of a targeting ligand can be increased, and SN38 is used as a small molecule cytotoxic load. The micromolecular prodrug has dual functions of active targeting and passive targeting, and can effectively improve the concentration in solid tumors, reduce toxic and side effects and improve the anti-tumor effect under the mediation of related receptors.

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 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 present disclosure provides double stranded ribonucleic acid (dsRNA) agents for inhibiting expression of a target gene, comprising an antisense strand which is complementary to the target gene; a sense strand which is complementary to the antisense strand and forms a double stranded region with the antisense strand; at least one alpha-v-beta-6 (αvβ6) integrin targeting ligand that mediates delivery to muscle tissue conjugated to at least one strand; and at least one in vivo delivery enhancing moiety conjugated to one or more internal positions on at least one strand. The present disclosure also provides compositions comprising such dsRNA agents, and methods of use thereof for treating a subject having a disorder that would benefit from reduction in expression of the target gene.

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 present invention provides a pharmaceutical composition for inhibiting the expression of the NFKBIZ gene and its application, belonging to the technical field of biomedicine. The present invention designs double-stranded nucleic acid molecules capable of targeting and regulating the expression of the NFKBIZ gene. By verifying the gene regulation efficiency of the nucleic acid molecules, multiple nucleic acid molecules are screened to be able to inhibit the expression of the NFKBIZ gene, and the purpose of efficiently inhibiting the expression of IκB-ζ protein is achieved at the protein level. At the same time, the present invention verifies the application of the pharmaceutical composition formed by coupling the above nucleic acid molecules and targeting ligand molecules in ophthalmic diseases. This pharmaceutical composition can solve the problems of low delivery efficiency and poor therapeutic effect of existing small molecule immunomodulatory drugs, endow small nucleic acid drugs with tissue-targeted delivery function, and has advantages such as long drug effect time and small side effects; in addition, the composition of the pharmaceutical composition is simple and easy to synthesize, and has good prospects for translational application.

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 disclosure relates to the field of genetic engineering technology, and more specifically, to a targeting ligand. The targeting ligand provided herein forms a siRNA conjugate with a specific small interfering RNA sequence, which targets ANGPTL3 and degrades ANGPTL3 gene transcripts in cells, thereby reducing ANGPTL3 protein expression. Therefore, the siRNA conjugate formed with the targeting ligand provided herein can be used to prevent and / or treat dyslipidemia.

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.

The invention relates to the technical field of drug loading systems, and discloses a nanoparticle applied to photodynamic therapy and a preparation method thereof.The nanoparticle is of a core-shell-crown composite structure and sequentially comprises an inner core layer, an outer core layer, an inner shell layer and an outer shell layer from inside to outside, the inner core layer is composed of NaYF4 up-conversion nanoparticles, and the outer core layer is composed of NaYF4 up-conversion nanoparticles; the middle layer is a mesoporous Zr-MOF layer; the shell layer is a pH responsive polymer layer which is formed by connecting a polyethylene glycol-polycaprolactone block copolymer with folic acid through a hydrazone bond; the targeting canopy layer comprises double targeting ligands, and the double targeting ligands are respectively a bicyclo [6.1. 0] nonyne functionalized iRGD peptide and an azide functionalized anti-EGFR (epidermal growth factor receptor) nano antibody 7D12. The nanoparticles have the advantages of high stability, strong targeting property, high photosensitizer loading and the like, and can efficiently generate active oxygen.

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.