44 results about "Molecular targeting" patented technology

Disclosed are compositions and methods useful for targeting and internalizing molecules into cells of interest and for penetration by molecules of tissues of interest. The compositions and methods are based on peptide sequences that are selectively internalized by a cell, penetrate tissue, or both. The disclosed internalization and tissue penetration is useful for delivering therapeutic and detectable agents to cells and tissues of interest.

The invention provides an application of a super enhancer inhibitor JQ-1 in preparation of peripheral artery disease related drugs, relates to the technical field of biomedicine, and discloses a core effect of the super enhancer inhibitor JQ-1 in peripheral artery disease ischemia repair. The traditional Chinese medicine composition can significantly accelerate blood flow recovery of ischemic limbs, up-regulate mRNA and protein expression of a vascular marker CD31 in gastrocnemius muscle tissues, effectively increase vascular density and promote angiogenesis. Aiming at the defects of the existing treatment means in the aspect of ischemic tissue angiogenesis, the application provides a brand new molecular targeted treatment scheme for high-risk groups such as patients with diabetes-related peripheral artery diseases, and can significantly reduce the risk of lower limb amputation and the incidence rate of related cardiovascular adverse events such as coronary heart disease and stroke; the technical blank of specific targeted therapy of peripheral artery diseases is filled, a solid scientific basis and a key direction are provided for research and development of novel drugs, and the specific targeted therapy method has extremely high clinical application value and wide research and development prospects.

The present application relates to the field of biological medicine and clinical diagnosis, and more particularly, the present application relates to a polypeptide having binding affinity to AXL protein and application thereof; the polypeptide has binding affinity to AXL protein, and therefore can be used for detecting AXL protein, so that the polypeptide has diagnostic or therapeutic use as a drug or molecular targeting reagent.

Targeting immunosuppressive B cell populations using bispecific or multivalent targeting molecules presents a potential pathway for therapeutic interventions that effectively modulate antitumor immune responses and improve therapeutic outcomes. Therefore, we provide engineered antibody-based therapeutics that can effectively and selectively target immunosuppressive B cell populations for the treatment of cancer. [Solution] A multispecific antibody is provided comprising a CD19 antigen-binding component configured to bind to CD19 and a CD38 antigen-binding component configured to bind to CD38, wherein the CD19 antigen-binding component comprises an antibody or an antigen-binding fragment thereof, and the CD38 antigen-binding component comprises an antibody or an antigen-binding fragment thereof.

The present invention addresses the problem of providing a novel combination therapy having a potent antitumor effect and few side effects. The present invention provides an antitumor agent containing zipalertinib or a salt thereof as an active ingredient and used so as to be administered to a cancer patient in combination with an additional antitumor agent, wherein the additional antitumor agent is at least one selected from the group consisting of molecular targeting agents, immune checkpoint inhibitors, and antibody-drug conjugates.

Methods, techniques, and kits are provided herein for purifying cells using molecular targeting, at a cellular or subcellular level. The techniques comprise labeling a biological sample comprising cells with a probe capable of producing a protective barrier. The barrier is deposited onto the surface of the labeled cells or structures, to protect and retain the biological material under the barrier. A micropurification solution is applied to the biological sample, wherein the micropurification solution degrades, digests, or otherwise processes cells not covered by the barrier, allowing isolation of the target cells. In some aspects, a plurality of probes, each specific to a different target, may be used. The techniques may be performed without the need for complex instrumentation involving microscopy.

This invention provides hepatocellular carcinoma-derived growth factor (HDGF) as a target for resistance to tyrosine kinase inhibitors and its related applications. This invention provides the application of HDGF as a target in screening and / or preparing drugs that can improve resistance to tyrosine kinase inhibitors in patients. This invention discovers that high expression of HDGF is one of the mechanisms of resistance to molecularly targeted drugs such as gefitinib and other tyrosine kinase inhibitors. Targeting HDGF can effectively improve resistance to gefitinib in NSCLC and enhance therapeutic efficacy.

The invention provides a detection reagent for LXOL2 gene expression quantity and application of LXOL2 as a rheumatoid arthritis treatment target, and relates to the technical field of biological medicines. According to an extracted total RNA sequence, a specific PCR primer is designed and synthesized, an RT-qPCR technology and a sequencing method are utilized, the expression of the LXOL2 in human synovial fibroblast-like cells is found to be remarkably increased, it is proved that the LXOL2 can be applied to preparation of a preparation for auxiliary diagnosis, treatment or prognosis evaluation of rheumatoid arthritis, meanwhile, Si-LOXL2 small in interference with the gene is designed and synthesized, and the application prospect is wide. According to the present invention, the expression of the LXOL2 gene can be knocked down, the expression of pro-inflammatory factors TNF-alpha, IL-1beta and IL-6 can be significantly inhibited, the expression of anti-inflammatory factors TGF-beta can be promoted, and the gene can be used as the RA molecular targeting treatment tool;

The invention discloses a red light-pH dual-response targeted antibacterial and anti-inflammatory nanoparticle as well as a preparation method and application thereof. The nano-particle is prepared from the following raw materials: a porphyrin-zirconium metal organic framework carrier, an antibacterial agent, NO donor molecules and a targeting ligand, the mass ratio of the porphyrin-zirconium metal organic framework carrier to the antibacterial drug to the NO donor molecule to the targeting ligand is 1: (0.8-1.2): (0.3-1): (1-3). The red light-pH dual-response targeted antibacterial and anti-inflammatory nano-particle is of a layered composite structure of'carrier-functional molecule-targeted shell ', and has high efficiency, safety and practicability.

Disclosed is a multi-specific molecule targeting CD16A expressed on NK cells and HER2 or GPC3 expressed on tumor cells, enhanced by a complex formed by IL-15 and IL-15Rα contained in the multi-specific molecule. Also disclosed are polypeptides, compositions and methods relevant to the multi-specific molecule.

The invention provides application of a super enhancer inhibitor JQ-1 in preparation of a medicine for treating wound healing disorder related diseases. Relates to the technical field of biomedicine, the promotion effect of the super enhancer inhibitor JQ-1 in wound healing and repairing is disclosed for the first time, the super enhancer inhibitor JQ-1 is competitively combined with BET protein bromodomain, combination of the super enhancer inhibitor JQ-1 and acetylated histone is blocked, and super enhancer driven gene transcription is inhibited. Skin regeneration can be obviously accelerated, the wound healing time is shortened, and the healing degree is improved. Aiming at the pain point that the existing wound healing therapy is limited in effect, the invention provides a brand-new molecular targeted therapy scheme for people, such as diabetic patients and old people, which are easy to cause abnormal wound healing, can effectively reduce serious sequelae, such as amputation, and provides a scientific basis and a key direction for developing a novel medicine for promoting wound healing; the technical blank in the related treatment field is filled up, and important clinical application value and research and development prospects are achieved.

The invention belongs to the technical field of biological medicine, and provides a novel gold nanoparticle-based targeting preparation as well as a preparation method and application thereof. The targeting preparation provided by the invention contains a gold nanoparticle core, a connecting molecule, a targeting ligand and a therapeutic agent, the connecting molecule and the targeting ligand sequentially modify gold nanoparticles, the therapeutic agent is loaded at the drug loading capacity of 1-50wt%, and the mass ratio of the targeting ligand to the gold nanoparticles is (1: 5)-(1: 100). The targeting preparation provided by the invention can efficiently cross the blood brain barrier, obviously reduce Abeta deposition in the brain, is high in enrichment degree of a targeting region in the brain, can down-regulate miR-146a-5p to inhibit neuroinflammation, and can be used for treating neurodegenerative diseases.

The invention provides a small peptide for preventing and treating colon cancer and application thereof, and belongs to the technical field of biological medicine. Through structural simulation and functional verification, a polypeptide capable of specifically inhibiting G3BP1 lactylation in colon cancer cells in a targeted manner is screened out. The polypeptide inhibits the lactic acid modification level of G3BP1 by simulating a G3BP1 lactic acid recognition site and competitively combining with lactic acid enzyme, so that the G3BP1 mediated autophagy process is blocked, and finally proliferation and migration of colon cancer cells are inhibited. In-vitro cell experiments (including cell proliferation, migration and autophagy level analysis) and in-vivo transplantation tumor animal experiments prove that the oligopeptide can significantly inhibit growth and tumor formation of colon cancer cells. The discovery provides a new strategy and candidate drug molecules for molecular targeted therapy of colon cancer.

The present invention provides a method for efficiently producing lipid particles that contain an active component and in which the surfaces of the lipid particles are conjugated with a ligand specific to a target cell. The method for producing lipid particles with a ligand conjugated to the surface thereof includes: (1) a step for mixing an organic solvent phase (a) containing a lipid component, an aqueous phase (b) containing an active component, and an organic solvent phase or an aqueous phase (c) containing a molecule (targeting lipid molecule) in which a ligand specific to a target cell and a lipid are covalently bonded; and (2) a step for purifying the mixture obtained in step (1).

Disclosed herein are compositions and methods for deploying interventional agents into constrained biological states using non-crystalline amorphous iron oxide nanoparticles (NAIONPs). The NAIONPs comprise coordination-stabilized, aqueous colloidal dispersions lacking long-range crystalline order and presenting surface-accessible coordination sites for reversible or covalent association with one or more interventional agents. The compositions are configured to modify the biological context in which an interventional agent is presented, enabling functional engagement of agents whose deployment is limited when administered in isolation due to factors including impaired biodistribution, reduced stability, stress sensitivity, immune-mediated clearance, altered cellular responsiveness, or non-optimal exposure conditions. Interventional agents may include polynucleotides, peptides, proteins, small molecules, targeting moieties, radiologic agents, or combinations thereof. The disclosed compositions and methods are applicable to in vivo, ex vivo, and in vitro biological systems, including oncologic disease states such as primary tumors, metastatic disease, hematologic malignancies, and treatment-refractory cancers.

The application discloses application of a PI3K-gamma-delta signal path inhibitor in preparation of a product for treating central nervous system leukemia and the product, and solves the technical problem that the prior art lacks a molecular targeting product for acute lymphoblastic leukemia with CNSL which has better effect. The application comprises: application of the PI3K-gamma-delta signal path inhibitor in preparation of a product for treating acute lymphoblastic leukemia with central nervous system leukemia, and application of the PI3K-gamma-delta signal path inhibitor in preparation of a product for inhibiting proliferation, invasion and migration of acute lymphoblastic leukemia with central nervous system leukemia. The application also comprises a product of the PI3K-gamma-delta signal path inhibitor. The application discloses that central nervous system leukemia is closely related to an expression level of MSLN, and the PI3K-gamma-delta signal path inhibitor can inhibit the infiltration degree of acute lymphoblastic leukemia with central nervous system leukemia by reducing the expression level of MSLN, and prolong the survival time.

The invention belongs to the technical field of biomedical engineering and cell therapy, and particularly relates to a preparation method of a mesenchymal stem cell exosome capable of improving an anti-inflammatory function. The core is a collaborative design of composite biochemical pre-stimulation and inflammatory microenvironment response type three-function targeting anchoring. A tumor necrosis factor-alpha with a concentration of 5-8 ng / mL, a resveratrol derivative with a concentration of 2-5 [mu] mol / L and glutathione with a concentration of 10-20 [mu] mol / L are adopted for reverse synergistic pre-stimulation, such that an anti-inflammatory pathway is activated; a vascular cell adhesion molecule-1 targeting domain-matrix metalloproteinase-9 sensitive connecting arm-LL-37 anti-inflammatory domain fusion polypeptide is anchored, so that precise targeting and response release are realized. According to the method, the problems of insufficient anti-inflammatory activity, poor targeting and off-target of the exosome are solved, the enrichment amount of an inflammatory site is increased by 2.5-4 times, the TNF-alpha inhibition rate reaches 90%-95%, and the exosome is suitable for treating inflammatory diseases.

Disclosed herein are modifications of polynucleic acid molecules such as inhibitory polynucleic acid molecules and pharmaceutical compositions comprising modified polynucleic acid molecules. Further, provided herein are methods for utilization of modified polynucleic acid molecules as well as methods for suppressing an expression of gene targeted by the modified polynucleic acid molecules.

The present disclosure provides a modified bispecific molecule that targets (a) a tumor-specific mutant peptide or mutation-associated neoantigen (MANA) presented by human leukocyte antigens (HLA) on the surface of target cancer cells; and (b) a surface protein (e.g., CD3) expressed on effector immune cells (e.g., T cells), as well as a method of using the molecule in cell therapy to diagnose, prevent, and / or treat human diseases including cancer. The bispecific molecule is modified to additionally include domain orientation modifications, linker modifications, and functional moieties including, e.g., Fc fragments, serum albumin, and / or polyethylene glycol (PEG) groups, which can improve efficacy, therapeutic index, half-life, and ease of manufacture while maintaining functionality and specificity in the treatment of diseases such as cancer.

The application belongs to the technical field of biological medicine, and particularly relates to a pharmaceutical use of a Hedgehog pathway inhibitor in preventing and treating vascular remodeling and restenosis after an arterial bypass operation and improving the survival rate of a coronary heart disease patient after the arterial bypass operation. The abnormal proliferation of smooth muscle cells driven by endothelial cell activation can be obviously inhibited by the Hedgehog pathway inhibitor GDC-0449 intervention, and the inflammatory reaction can be effectively reduced. In the in-vivo experiment, the local application of GDC-0449 to the bypass artery can significantly relieve the remodeling and stenosis of the bypass artery, and provide a theoretical basis and strong support for the molecular targeted treatment strategy of the vascular remodeling and failure after the arterial bypass operation.

According to the present invention, the R-lycosin-I / porphyrin coupling phototherapy nanometer aggregate (R-LTNPs) is designed; the multifunctional material consists of polypeptide R-lycosin-I for inhibiting tumor growth and migration and inducing apoptosis, and a porphyrin part capable of realizing fluorescence imaging, photodynamic therapy (PDT) and photothermal therapy (PTT). Through covalent coupling, the nanospheres are uniformly distributed, and excellent phototherapy performance, colloidal stability and tumor targeting specificity are shown. In-vitro experiments use B16-F10 melanoma cells show that R-LTNPs retains the intrinsic cytotoxicity and cellular uptake efficiency of peptides, and can induce strong light to activate phototoxicity under light irradiation. In in-vivo experiments, the combination of R-LTNPs and light irradiation realizes remarkable tumor growth inhibition and ablation effects which exceed the effect of single-drug treatment. According to the invention, a nano assembly material is reasonably designed, and the nano assembly material shows excellent potential in the aspect of promoting combined oncology, provides a general framework for integrating molecular targeting, imaging and multi-modal treatment, and is used for a next-generation anti-cancer strategy.

The present invention provides a small molecule compound targeting a folate receptor, a preparation method, a composition, and a use. Specifically provided is a compound represented by formula (I) or a pharmaceutically acceptable salt thereof. The compound or the pharmaceutically acceptable salt thereof provided by the present invention can be used as a small molecule targeted fluorescent contrast agent for adjuvant surgical treatment, and has a novel structure and good targeting performance. A near infrared fluorescence capture system provided by the present invention facilitates tumor diagnosis and treatment and has good application prospects.

This invention discloses a molecular targeting capture instrument based on SPR detection, comprising an instrument frame, a sampling and collection module, a flow path rectification and signal acquisition module, and a liquid path system. The sampling and collection module includes independently driveable sampling and collection mechanisms. The sampling needle and collection needle are connected to independent motors via synchronous belts to achieve X, Y, and Z-axis motion. The flow path rectification and signal acquisition module integrates an SPR detection chip and a flow cell. The liquid path system includes a plunger pump, a reservoir ring, a six-way valve, and multiple three-way valves, connected to the sampling needle, collection needle, and flow path rectification and signal acquisition module via pipelines to form a closed fluid pathway. This invention, by fixing target points on the chip surface, can specifically capture and recover components with affinity for the target from complex samples. SPR technology monitors the entire process in real time, and the optimized flow path system enhances tolerance to complex samples, making it suitable for screening effective components in complex systems such as traditional Chinese medicine extracts and serum.

Provided herein are artificial microRNA (miRNA) molecules for treating synucleinopathies. In some embodiments, these miRNA molecules target the expression of SNCA protein. Further provided herein are expression constructs, vectors (e.g., rAAV), cells, viral particles, and pharmaceutical compositions containing these artificial miRNA molecules. Still further provided herein are methods and kits related to the use of these miRNA molecules, e.g., for treating synucleinopathies including Parkinson’s disease, multiple system atrophy, or Lewy body dementia.

The application provides a small peptide for preventing and treating colon cancer and an application thereof, and belongs to the technical field of biological medicine. Through structure simulation and function verification, a polypeptide capable of specifically targeting and inhibiting G3BP1 lactylation in colon cancer cells is screened. The polypeptide competitively binds to lactylase by simulating the G3BP1 lactylation recognition site, thereby inhibiting the lactylation modification level of G3BP1, blocking the autophagy process mediated by G3BP1, and finally inhibiting the proliferation and migration of colon cancer cells. Through in vitro cell experiments (including cell proliferation, migration and autophagy level analysis) and in vivo tumor transplantation animal experiments, it is proved that the short peptide can significantly inhibit the growth and tumor formation of colon cancer cells. This finding provides a new strategy and candidate drug molecule for the molecular targeted treatment of colon cancer.

This invention discloses a mitochondrial uncoupling agent prodrug with endothelial cell targeting, its preparation method, and its application, relating to the field of biomedical technology. The prodrug is covalently coupled to a vascular cell adhesion molecule-1 targeting polypeptide (amino acid sequence FAKELMEEFEKW), a reactive oxygen species-sensitive thioacetate linker, and the mitochondrial uncoupling agent OPC-163493. This invention utilizes the active enrichment effect of the targeting polypeptide on inflamed pulmonary vascular endothelial cells, overcoming the off-target defects of non-specific distribution in existing small molecule drugs; simultaneously, it utilizes the specific cleavage characteristics of the thioacetate linker in a microenvironment rich in reactive oxygen species to achieve precise in-situ drug release. This prodrug can effectively reduce mitochondrial reactive oxygen species generation, inhibit endothelial cell apoptosis, significantly reduce pulmonary vascular permeability, and alleviate pulmonary edema, possessing significant clinical application value in the preparation of drugs for treating acute lung injury or acute respiratory distress syndrome.

The invention relates to a space-time cascade type antibody coupling medicine as well as a preparation method and application thereof, and belongs to the technical field of antibody coupling medicines. In order to solve the problem of low activation efficiency caused by heterogeneity of enzyme expression in a tumor microenvironment in the current antibody-coupled drug adopting polypeptide as a connexon, the invention provides a space-time cascade antibody-coupled drug which comprises a G molecule and an R molecule which are administrated step by step, the G molecule comprises a monoclonal antibody and a trans-cyclooctene group which are covalently connected, and the R molecule comprises a difunctional PEG connexon, trans-tetrazine, a short chain which cannot be enzymolyzed and a toxic molecule which are sequentially connected. The time-space cascade design is adopted, through the mechanism of G molecule targeted enrichment-> TCO anchor point exposure-> R molecule perfusion binding-> TCO-Tz ultrafast click reaction toxin release, instant high-concentration delivery of toxin is achieved, dependence on intracellular enzymolysis or internalization is avoided, the anti-tumor effect is remarkably enhanced, and systemic toxic and side effects are reduced.

Disclosed herein are polynucleic acid conjugate compositions comprising a polynucleic acid molecule and one or more targeting moiety such as an asialoglycoprotein receptor targeting moiety and a lipophilic moiety, for targeted delivery of the polynucleic acid molecule to a target cell. Disclosed herein are also pharmaceutical compositions comprising polynucleic acid conjugate composition. Further, provided herein are methods and / or uses of polynucleic acid conjugate composition and pharmaceutical composition comprising polynucleic acid conjugate composition described herein.

The invention belongs to the field of molecular targeted therapy, and particularly relates to a small-molecule inhibitor SUN-RASD01 aiming at KRASG12D and application of the small-molecule inhibitor SUN-RASD01 in inhibition of pancreatic cancer and colorectal cancer cells. The invention provides a structural formula of a small-molecule inhibitor SUN-RASD01 aiming at KRASG12D. The small-molecule inhibitor can inhibit KRASG12D protein from inhibiting pancreatic cancer and colorectal cancer cell proliferation. Compared with a known inhibitor, the KRASG12D small-molecule inhibitor provided by the invention has strong affinity, can be used as a novel antitumor drug to thoroughly remove tumors, and has a wide application prospect.