82 results about "Receptor targeting" patented technology

The invention belongs to the technical field of genetic engineering and biological medicine, and particularly discloses a cascade response type nano-particle with a microenvironment remodeling function and a preparation method and application of the cascade response type nano-particle. The nanoparticle provided by the invention adopts a bionic hybrid membrane engineering strategy: an inner core is formed by loading an exosome inhibitor on a nano material, and the surface is covalently coupled with M2 type macrophage specific targeting peptide; the outer layer coats a macrophage membrane and active oxygen response type liposome composite membrane layer through a co-extrusion technology, and is loaded with a TLR agonist. Animal experiments show that after being injected through caudal vein, the nano-particles are enriched at a tumor site in a targeted manner through homing receptors such as membrane surface integrin alpha4beta1 and the like, and outer membrane cracking is triggered in a high-ROS tumor microenvironment, so that space-time controlled release of a TLR agonist and targeted phagocytosis of an exosome inhibitor by macrophages guided by a targeted peptide are realized. The anti-tumor synergistic effect is achieved through multiple regulation and control mechanisms, and an effective treatment strategy is provided for tumor immunotherapy.

The invention discloses a leukemia targeted therapy preparation as well as a preparation method and application thereof. Comprising a DNA nanoflower carrier targeting leukemia cells through a PTK7 receptor and benzene arsenic oxide loaded on the carrier. The DNA nanoflower carrier is obtained by rolling circle amplification, and a nucleic acid aptamer complementary sequence of targeted binding leukemia cells is introduced into a template chain subjected to rolling circle amplification. The preparation method comprises the following steps: modifying sulfydryl onto a DNA nanoflower by using DNA-Dithiol, then breaking a disulfide bond by using reduced glutathione to expose the sulfydryl, and loading benzene arsenic oxide onto the DNA nanoflower through a reaction between trivalent arsenic and the sulfydryl. The structure of the DNA nanoflower has a high surface area and high porosity, and can load a large amount of PAO, so that the killing performance on cancer cells is enhanced; the aptamer sgc8 sequence is introduced into the DNA nanoflower, so that the targeting of the DNA nanoflower to cancer cells is effectively realized; the preparation also has the advantages of being good in thermodynamic stability, easy to store, excellent in biocompatibility and the like, and has a very good application prospect.

The invention relates to the field of biological medicine, in particular to a hair follicle targeted delivery system and hair growth and hair loss prevention cosmetics, the hair follicle targeted delivery system comprises: a lipid nanoparticle core which is internally loaded with a bioactive component with hair growth and hair loss prevention effects; the hair follicle targeting molecule can specifically recognize and bind to a receptor on the surface of a hair follicle cell; a targeting anchoring conjugate composed of a linker covalently linked to the hair follicle targeting molecule and an anchoring lipid; wherein the targeting anchoring conjugate is embedded into the lipid bilayer of the lipid nanoparticle core through the anchoring lipid, so that the hair follicle targeting molecule is displayed on the surface of the lipid nanoparticle core. According to the application, through an innovative targeted anchoring conjugate structure, the targeting property and enrichment efficiency of hair growth and hair loss prevention active ingredients on hair follicle tissues can be remarkably improved, and the effect that a medicine accurately acts on a focus part is ensured, so that the number of hair follicles at an alopecia areata modeling part can be remarkably increased.

The present disclosure relates to compounds of Formula (I), or a pharmaceutically acceptable salt thereof, stereoisomer thereof, analog thereof, solvate thereof, prodrug thereof, and / or tautomer thereof, as well as pharmaceutical compositions including such a compound, wherein the variables are as defined in the specification. Also described are method of using such compounds and pharmaceutical compositions to treat GLP-1 associated diseases, disorders, or conditions.

The present invention provides an oncolytic virus vector containing a sequence encoding IL-4 receptor targeted cargo protein, including IL-4 muteins and / or IL-13 muteins, the oncolytic virus encoded therefrom, the uses of the oncolytic virus for treating cancer.

The invention belongs to the technical field of biomedical imaging, and particularly discloses an in-vivo imaging method of an SAPAP3 gene defect disease model, which is characterized in that an effective dose of an S1PR1 receptor targeted radioactive probe is injected into the body of the SAPAP3 gene defect disease model. According to the method, an S1PR1 receptor targeting radioactive probe is utilized, the technical bottleneck that in-vivo and dynamic observation of the S1PR1 receptor cannot be achieved through an existing in-vitro technology is solved, and an indispensable visual tool and a quantitative evaluation means are provided for studying the neurobiological mechanism of related mental diseases such as obsessive-compulsive disorder and accelerating research and development of related drugs.

Methods are provided for attaching a mannose-binding C-type lectin receptor targeting moiety to a polymeric carbohydrate scaffold using an amide bond, which can be found between a leash, such as an amine-terminated leash, and the mannose-binding C-type lectin receptor targeting moiety. The disclosed compounds and compositions utilizing this amide bond provide highly stable compounds that significantly reduce loss of the mannose-binding C-type lectin receptor targeting moiety from the polymeric carbohydrate scaffold.

The application discloses a PROTAC compound with RORgamma t receptor targeted degradation and purposes thereof, which is a compound with a structure shown in a general formula (I) or a pharmaceutically acceptable salt thereof and a pharmaceutical composition thereof. e is a ligand capable of combining with an E3 ubiquitin ligase; the L is a linking group covalently combining at least one R e and at least one R W ; the R w is a target protein RORgamma t binding ligand; the application is based on the target point of RORgamma t and the PROTAC technology, and a series of RORgamma t-PROTACs are designed and synthesized for the first time. The mechanism is that the target protein ligand and the E3 ubiquitin ligase ligand are combined with POI and E3 ligase respectively, so as to form a ternary complex of "POI-PROTAC-E3 ligase". Then, the POI is marked with a ubiquitination label, and is degraded by a proteasome. The advantages of RORgamma t-PROTACs mainly include targeting of "undruggable proteins", small dosage, low toxicity, and difficulty in drug resistance. W -L-R e (I)

This invention relates to the field of biomedicine, and more particularly to a hair follicle-targeted delivery system and a hair growth and anti-hair loss cosmetic. The hair follicle-targeted delivery system comprises: a lipid nanoparticle core loaded with bioactive ingredients having hair growth and anti-hair loss effects; a hair follicle-targeting molecule capable of specifically recognizing and binding to receptors on the surface of hair follicle cells; and a targeting and anchoring conjugate consisting of a linker covalently linked to the hair follicle-targeting molecule and an anchoring lipid. The targeting and anchoring conjugate is embedded in the lipid bilayer of the lipid nanoparticle core via the anchoring lipid, thereby exposing the hair follicle-targeting molecule on the surface of the lipid nanoparticle core. This application, through its innovative targeting and anchoring conjugate structure, can significantly improve the targeting and enrichment efficiency of the hair growth and anti-hair loss active ingredients on hair follicle tissue, ensuring precise drug action on the lesion site, thereby significantly increasing the number of hair follicles in the alopecia areata modeling area.

The invention discloses a lipidosome composite hydrogel microsphere for repairing damaged intestinal mucosa and a preparation method thereof, LHMs (at) 4-OI is composed of hyaluronic acid modified targeted drug-loaded lipidosome, sodium alginate, hydrochloric acid treated sucralfate and a CaCl cross-linking agent, and rapid gel forming is carried out under the voltage of 11.0 KV through an electrospray technology. The microspheres have pH responsiveness and gastric juice digestion resistance, CD44 receptor targeting is achieved through hyaluronic acid modification, sodium alginate and Ca form an egg box structure to provide a three-dimensional network, and sucralfate enhances adhesion to isolate harmful substances. The preparation method comprises the steps of preparation of the drug-loaded liposome by a film hydration method, hyaluronic acid modification and electrospray crosslinking, is simple to operate and low in cost, and can be used for large-scale production. The microspheres can effectively load an anti-inflammatory drug 4-OI, inhibit expression of inflammatory factors and promote self-repair of damaged intestinal mucosa, and have wide application prospects in the fields of abdominal infection, inflammatory bowel diseases, colorectal cancer and the like.

The invention discloses a functionalized targeting fluorescent nanoprobe and application thereof in protein mutation analysis, and relates to the technical field of biology, the fluorescent nanoprobe comprises a targeting molecule-PEG hydrophilic bridging molecule and a matrix; the preparation method comprises the following steps: adding nano-seeds into fluorescent molecules to prepare fluorescent nano-particles, and stirring and mixing the fluorescent nano-particles with targeting molecules-PEG hydrophilic bridging molecules; the method is combined with deep learning to be applied to protein mutation analysis. The multifunctional integrated protein mutation receptor targeted fluorescent nanoprobe provided by the invention can accurately mark the position of a mutant protein at a single cell level, and can realize in-situ, real-time and dynamic living cell imaging of a tumor cell endogenous molecular mutant protein; and qualitative and quantitative analysis of tumor cell protein mutation can be realized through subcellular localization of the targeted fluorescent nanoprobe.

Provided are compounds, compositions, and methods for re-polarizing tumor-associated macrophages (TAMs), reducing macrophage-mediated inflammation, and treating diseases. The compound or pharmaceutical composition can be administered to a subject in need thereof, the compound comprising a polymeric carbohydrate backbone and one or more mannose-binding C-type lectin receptor targeting moieties, and the therapeutic agent comprising one or more reactive hydroxyl groups and being attached to the polymeric carbohydrate backbone via a cleavable linker. The cleavable linker can comprise one or more carbonate and / or disulfide moieties. Diseases to be treated can include cancer, autoimmune diseases, inflammatory disorders, non-alcoholic steatohepatitis (NASH), acute respiratory distress syndrome (ARDS), sepsis, coronavirus infection, influenza infection, cytokine storm, and other macrophage-related diseases.

The present invention relates to the field of TREM2 receptor drug screening, and specifically proposes a rapid screening method for TREM2 receptor drugs. The method mainly comprises: (1) fusing a halogenated alkane dehalogenase to the inactive end of the TREM2 receptor to construct a TREM2 recombinant protein with a directional immobilization function; (2) covalently modifying a separation medium with 6-bromohexanoic acid to obtain a surface-modified separation medium; (3) fully mixing the TREM2 recombinant protein with the 6-bromohexanoic acid-modified separation medium, and incubating the mixture to allow the TREM2 receptor to be directionally modified on the surface of the separation medium. The resulting TREM2 recombinant protein immobilized complex is further used to prepare a TREM2 receptor chromatographic column, which can specifically identify its ligand based on retention time, thereby realizing rapid screening of TREM2 receptor-targeting compounds in complex systems such as traditional Chinese medicine.

# imgabs0. The present invention discloses compounds of formula (I) and complexes thereof with radionuclides, which can recognize both the somatostatin type 2 receptor (SSTR2) and the cholecystoxin 2 receptor (CCK2R) and can be used in the diagnosis and treatment of diseases in which either or both receptors are overexpressed.

The application provides a folate receptor targeted drug, a metal complex and a preparation method and application thereof, and relates to the technical field of radio labeling. The folate receptor targeted drug has a structure as shown in formula I, and a metal complex is prepared after being labeled by a radionuclide. The folate receptor targeted drug or the metal complex provided by the application can be used for diagnosing and / or treating diseases with overexpression of folate receptors. The folate receptor targeted drug has the advantages of high in-vivo stability, strong specificity, good targeting property and the like.

The invention relates to the field of TREM2 receptor drug screening, and particularly provides a rapid screening method of TREM2 receptor drugs. The method mainly comprises the following steps: (1) fusing halogenated alkane dehalogenase subjected to specific mutation to an inactive terminal of a TREM2 receptor to construct a TREM2 recombinant protein with a directional immobilization function; (2) carrying out covalent modification on the separation medium by using 6-bromohexanoic acid to obtain a surface-modified separation medium; and (3) fully mixing the TREM2 recombinant protein with the 6-bromohexanoic acid modified separation medium, and carrying out incubation treatment, so that the TREM2 receptor is directionally modified to the surface of the separation medium. The obtained TREM2 recombinant protein immobilized complex is further used for preparing a TREM2 receptor chromatographic column, the TREM2 receptor chromatographic column can specifically recognize a ligand according to retention time, and rapid screening of TREM2 receptor targeted compounds in complex systems such as traditional Chinese medicine is achieved.

Provided are methods of treating myelodysplastic syndrome (MDS), oligoblastic acute myelogenous leukemia (O-AML), or chronic myelomonocytic leukemia (CMML) using 765IGF-MTX and other IGF-receptor-targeted agents, and formulations for delivering 765IGF-MTX and other IGF-receptor-targeted agents to patients. Also provided are pharmaceutical compositions for use in treating MDS, O-AML, and CMML.

Provided are a multifunctional genetically modified immune cell, and a preparation method and use therefor. The multifunctional gene modification vector carries an isolated nucleic acid. The isolated nucleic acid comprises: a first nucleic acid fragment, a second nucleic acid fragment and a third nucleic acid fragment. The first nucleic acid fragment, the second nucleic acid fragment and the third nucleic acid fragment are connected. The first nucleic acid fragment is used for encoding an antigen chimeric receptor targeting a NKp30 ligand. The second nucleic acid fragment is used for encoding a fusion protein, wherein the fusion protein comprises IL-15 and IL-15 Rα, and IL-15 is connected to IL-15 Rα. The third nucleic acid fragment is used for encoding a CXCR2 receptor. Therefore, the multifunctional genetically modified immune cell prepared by using the multifunctional gene modification vector can improve the specific killing ability, survival ability, proliferation ability and tumor infiltration ability of the immune cell, so that the clinical curative effect of the immune cell is further improved.

This application discloses a compound or a pharmaceutically acceptable salt thereof, said compound comprising a compound of formula (I) or a compound of formula (II). A radioactive element preparation comprising thereof and a radioactive element chelated therewith is also disclosed. Its use in the preparation of reagents targeting CXCR4, particularly CXCR4 tracers, more particularly in vivo CXCR4 tracers, or reagents that specifically bind to cells expressing CXCR4 is also disclosed. [Targeting Peptide-I]-Xaa1-X 1 (R 1 )L 1 -[Connector]-R x n1 (I), R x n1 -[Connector]-X 1 (R 1 )L 1 -Xaa1-[targeting peptide-II](II).

The invention discloses a T cell adapter constructed based on GAS6 as well as a preparation method and application thereof, and relates to the technical field of cellular immunity, and the structure of the T cell adapter comprises an LG1 structural domain of GAS6, a CD3 binding domain, a linker, a marker protein and a fluorescent protein. Through a natural ligand-receptor targeting mechanism, multi-module collaborative design and structural optimization, the problems of high toxicity, single function, complex production process and the like of traditional CAR-T and scFv-BiTE are solved. Experimental data show that the T cell adapter has the advantages of high specificity, controllable immune activation, long-acting stability, easiness in large-scale production and the like, and provides a safer and more efficient immunotherapy strategy for AXL high-expression solid tumors (such as pancreatic cancer, breast cancer, liver cancer, colorectal cancer, lung cancer and the like) and hematoma (acute myelogenous leukemia, chronic lymphocytic leukemia and the like).

The present application relates to the technical fields of biological medicine and cellular immunotherapy, and particularly relates to a signal conversion receptor targeting IL-10, an engineered macrophage and application thereof. The signal conversion receptor is composed of an extracellular domain and a transmembrane domain and an intracellular domain derived from TLR9, and the extracellular domain sequentially comprises a signal peptide, a HA tag and a specific binding domain of an IL-10 receptor alpha subunit from N-terminal to C-terminal. The present application further prepares an engineered macrophage SR CAR-M capable of specifically recognizing IL-10 and converting it into a TLR9 activation signal, which can induce macrophages to polarize to M1 type and has excellent phagocytosis and killing capacity for bladder cancer, breast cancer, lung cancer and melanoma cells, and can be used for preparing related tumor treatment drugs, overcoming the common problems of existing cell therapy, such as easy exhaustion, difficult infiltration and easy inhibition in solid tumors, and having significant clinical transformation potential.

The invention provides a GSH (glutathione) reduction response type targeted nano-drug based on chondroitin sulfate as well as a preparation method and application of the GSH reduction response type targeted nano-drug. Chondroitin sulfate with CD44 receptor targeting ability and an anti-cancer drug camptothecin are covalently linked through a disulfide bond sensitive to GSH, and the constructed novel targeting nano-drug can accurately recognize human colorectal cancer tumor cells highly expressed by a CD44 receptor in a targeting manner. Meanwhile, the high-concentration glutathione at the tumor site can oxidize and reduce the disulfide bond to cause the fracture of AC-CPT NPs, so that the effective release of the camptothecin medicine at the tumor site is realized, and the anti-tumor effect is further enhanced. The reduction response type targeting nano-drug prepared by the invention solves the problems of poor targeting and biological solubility and limited treatment effect of the traditional anti-cancer drug camptothecin, and provides an innovative strategy for realizing accurate targeting and efficient treatment of cancers.

This invention discloses a folic acid receptor-targeting compound and its uses, belonging to the field of pharmaceutical technology. The folic acid receptor-targeting compound is a compound of formula (I), its stereoisomer, its crystalline hydrate, its deuterated derivative, its solvate, its prodrug, or a pharmaceutically acceptable salt thereof: [target]-(L x ) s -R x (I), where [target] is a folic acid receptor-binding ligand; R x The chelating group is Ch or the prosthetic group is PG; s is an integer from 1 to 10; L x It contains at least one L 3 and with AA, L 1 L 2 or L 3 Arbitrary combinations are possible. The folic acid receptor-targeting compounds of this invention have low KD values ​​and strong affinity between the ligands and receptors, and can be used as folic acid receptor-targeted radiotherapy agents for imaging, diagnosis, and treatment of folic acid receptor (FR)-expressing tumors or cells.

The present disclosure relates to a chimeric receptor targeting mesothelin and its uses. The chimeric antigen receptor comprises a first fusion peptide and a second fusion peptide, wherein: the first fusion peptide comprises a mesothelin antigen-binding domain and a transmembrane domain; the second fusion peptide comprises a transmembrane domain, a cytoplasmic domain and a co-stimulatory domain. The chimeric antigen receptor of the present disclosure has good killing activity against mesothelin-expressing positive solid tumor cells.

The invention discloses a nano blocker for hyaluronic acid energy metabolism of a targeted CD44 receptor as well as a preparation method and application of the nano blocker. The nano blocker is a nano preparation obtained by modifying a polylactic acid-glycolic acid copolymer (PLGA) with hyaluronic acid (HA) and then coating the PLGA with nebivolol hydrochloride and 3-bromopyruvic acid, and the nano preparation is marked as NBP-coated PLGA-HA. According to the CD44 receptor targeted hyaluronic acid energy metabolism nano blocking agent disclosed by the invention, bidirectional blocking of basic respiration of tumor cells is realized by using a loaded mitochondrial oxidative phosphorylation (OXPHOS) inhibitor nebivolol hydrochloride and a glycolysis inhibitor 3-bromopyruvic acid; meanwhile, effector immune cells are synergistically enhanced to maintain systemic anti-tumor immunity, high efficiency and safety are shown in in-vitro and in-vivo experiments, and concept paradigm transformation is provided for nano-drug mediated tumor treatment based on energy metabolism.

The invention belongs to the technical field of medicines, and discloses a paclitaxel and silver nanoparticle loaded lipidosome nano-targeting preparation as well as preparation and application of the paclitaxel and silver nanoparticle loaded lipidosome nano-targeting preparation. According to the invention, nano-particles coated with silver nano-particles are prepared by adopting a film dispersion method. The nano-drug provided by the invention is helpful for solving the problems of poor water solubility, low bioavailability, poor tumor targeting property, strong toxic and side effects and the like of an anti-cancer drug paclitaxel and low bacterial uptake efficiency of an antibacterial drug Ag Nps, and provides a hyaluronic acid coated CD44 receptor targeted paclitaxel and Ag Nps co-loaded liposome nano-targeting preparation, so that the anti-tumor effect is improved. The preparation process is simple, the cost is low, the stability is good, and the repeatability is high.

The invention belongs to the technical field of gene engineering, and provides Hsp60 receptor targeted recombinant lactobacillus plantarum as well as a construction method and application thereof, lactobacillus plantarum is taken as a host, pPG612 is taken as an expression vector, and CsgB gene or CsgF gene is expressed. The two engineering probiotics can express target protein and can be stably expressed on the surfaces of thalli, the AB.9 intestinal epithelial cells can be effectively adhered, and the adhesion and invasion of the A.veronii to the AB.9 cells can be inhibited. And secondly, the engineering probiotics LP-pPG-CsgB and LP-pPG-CsgF can promote the proliferation of dendritic cells, T lymphocytes and B lymphocytes, and improve the IgT secretion of intestinal mucus. The engineering bacteria can be competitively combined with an intestinal epithelial cell Hsp60 receptor, down-regulate p65 expression, inhibit NF-kappa B signal channel activation, regulate intestinal tight junction protein redistribution and down-regulate proinflammatory factor expression through a TLR4 / TLR5 dependent NF-kappa B signal channel, and the engineering bacteria can increase the abundance of effective microbial communities in the intestinal tract of the snakeheaded fish, so that the growth of the snakeheaded fish is promoted, and the growth of the snakeheaded fish is promoted. And the flora can transfer, mediate and activate immune response through a feeding environment.

The invention provides a preparation method and application of a multifunctional targeting nano material for treating various cancers. A biotin derivative with a biotin receptor targeting capability is modified on the surface of polycyclodextrin, and is mixed and assembled with a Golgi apparatus targeting photosensitizer and a PD-L1 in-situ inhibitor, so that the constructed novel multifunctional targeting nano material can accurately recognize various tumor cells in a targeting manner, and the enrichment of the photosensitizer at a tumor part is increased; the accumulation in the golf apparatus can be further realized, and the structure and the function of the golf apparatus can be obviously damaged. In addition, the nano drug delivery system can also realize effective PD-L1 down-regulation, and the photodynamic synergistic immune anti-tumor effect is further enhanced. The novel multifunctional targeted nano drug-loading system prepared by the invention solves the problems of poor targeting and biological solubility and limited immune response ability and treatment effect of the body of the traditional photosensitizer, and provides an innovative strategy for realizing targeted photodynamic synergistic immunotherapy of cancers.

The invention discloses a sentinel lymph node nano tracer and a preparation method and application thereof. The sentinel lymph node nano tracer is prepared from the following raw materials: a quantum dot material with near-infrared two-region luminescence characteristic, an amphiphilic polymer, a catalyst, a diamino polymer, a macrophage CD206 receptor targeting molecule and a temperature-sensitive polymer. Wherein the carboxyl group ratio of the macrophage CD206 receptor targeting molecule to the temperature sensitive polymer is (500 to 1000): (100 to 5000). The nano tracer integrates the high-resolution imaging advantage of quantum dots, the temperature response type aggregation characteristic and the receptor-mediated targeted delivery mechanism, can effectively prolong the developing time window while realizing accurate positioning of sentinel lymph nodes, and can provide a new design idea for developing intelligent response type surgical navigation probes; good application prospects are realized.

The invention discloses a cell membrane bionic magnetic nano-microsphere based on cannabinoid receptor CB2 receptor targeting, a preparation method of the cell membrane bionic magnetic nano-microsphere and application of the cell membrane bionic magnetic nano-microsphere to analgesic screening. The cell membrane bionic magnetic nano-microsphere takes a surface aldehyde group modified magnetic nano-microsphere as a core; a cell membrane of a high-expression cannabinoid receptor CB2 is wrapped on the surface of a magnetic bead by using a covalent bond binding method, a potential agonist is screened based on ligand-receptor affinity interaction, the active ligand of the cannabinoid receptor CB2 is efficiently captured by using a bionic magnetic nano material fishing technology, active components can be rapidly and sensitively screened out, and the application prospect is wide. The method is simple in operation, reduces analysis steps and time, improves analysis accuracy, remarkably improves separation efficiency and specificity of trace active components in a complex system by adopting collaborative innovation of a magnetic nano material and a biomimetic membrane technology, and has a great application prospect.