127 results about "CXCR4" patented technology

The invention discloses a mesenchymal stem cell membrane bionic nano-enzyme for targeted therapy of Parkinson's disease as well as a preparation method and application of the mesenchymal stem cell membrane bionic nano-enzyme. The mesenchymal stem cell membrane bionic nano enzyme comprises an inner core and a mesenchymal stem cell membrane, wherein the inner core is composed of mesoporous polydopamine nanoparticles, and the mesenchymal stem cell membrane coats the inner core. The medicine contains the mesenchymal stem cell membrane bionic nano enzyme. The mesenchymal stem cell membrane bionic nano-enzyme disclosed by the invention shows good biocompatibility, and can be homed to a Parkinson disease region in the brain under the mediation of CXCR4 and VLA-4 specific membrane proteins. In addition, through the CD47 membrane protein expressed on the surface, the removal of the immune system can be avoided, so that the action time in the body is prolonged. The nano-enzyme is helpful for eliminating reactive oxygen free radicals, reducing oxidative stress level and reducing damage of neuroinflammation to dopaminergic neurons, so that safe and efficient treatment of Parkinson's disease is realized.

The invention discloses a preparation method and application of a novel hybrid extracellular vesicle. According to the invention, vesicles derived from endothelial cells and neutrophil cells are combined with deferoxamine, and a biological mixed nano vesicle platform (DFO (HEVS)) is developed to solve the problem of diabetes wound healing. According to the dual-targeting system, DFO is accurately delivered to a wound part by utilizing CXCR4 mediated endothelial cell homing and beta2 integrin dependent inflammation tropism, DFO (at) HEVs activates and recovers vascular regeneration through HIF-1alpha / VEGF, ferroptosis is inhibited through Nrf2 / GPX4 signal transduction, macrophages are reprogrammed into a repair promoting M2 phenotype, and oxidative stress-inflammation-ferroptosis circulation is effectively broken.

The invention discloses a multichannel tissue-derived neutrophil detection chip and an application system, the chip is a multichannel detection chip integrating migration-related markers and functional markers, rapid and synchronous identification of neutrophil tissue sources is realized, the migration-related markers are CD62L and CXCR4, the functional markers are CD44 and MPO, and the migration-related markers are CD62L and CXCR4. According to the method, migration related markers and functional state markers are subjected to integrated and collaborative analysis, tissue sources are locked from the cell state and function two dimensions, four-channel parallel detection is performed, and the tissue sources of the neutrophil are accurately judged through expression profile modes of the four components instead of a single marker, so that the neutrophil detection accuracy is improved. According to the method, the neutrophil tissue source is rapidly, synchronously and accurately identified, the technical bottleneck of neutrophil tissue source detection is broken through, high efficiency, accuracy and universality are achieved, and an efficient and accurate tool is provided for immune mechanism research and clinical diagnosis.

The present invention relates to antibodies or antigen binding fragments thereof that specifically bind to CXCR4. The invention also relates to said antibodies for use in therapy, in the treatment of cancer, and in the treatment of solid tumors. The invention also relates to pharmaceutical compositions comprising said antibodies, nucleic acids encoding said antibodies, vectors comprising said nucleic acids, and host cells comprising said nucleic acids or vectors.

The invention provides in-situ forming fluid bionic hydrogel as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The invention provides an injectable GelSSO / PDA (at) SDF fluid bionic niche, after in-situ photo-crosslinking, preferential and sustained release of PDA (at) SDF NPs initiates early signal amplification, which recruits EPCs and MSCs through an SDF-1 alpha / CXCR4 axis, promotes activation of the angiogenic vascular niche through an AKT signal, and repolarizes macrophages to a regenerated M2 phenotype. Subsequently, the gradual degradation of the bionic niche triggers the stable release of SSO, and the later signal is further amplified to form an osteogenic niche with transcriptional activity, thereby maintaining the MAPK / ERK-mediated MSCs osteogenic differentiation. The fluid bionic niche can form a niche conforming to defects through photopolymerization, the local immune imbalance and endogenous progenitor cell recruitment are corrected in the early stage, then formation of new vessels and lamellar bones is promoted, and finally vascularization regeneration of diabetic skull defects is achieved.

The present invention provides CXCR4 inhibitors of formula (I) and pharmaceutically acceptable salts thereof, as well as methods of using them in the treatment of neurological and CNS diseases, disorders, and conditions. The provided compounds are inhibitors of CXCR4 and are therefore useful for treating one or more disorders associated with CXCR4 activity. Thus, in certain embodiments, the present invention provides a method for treating a CXCR4-mediated disorder, comprising administering to a patient in need thereof a CXCR4 inhibitor described herein, such as a compound of formula I or a pharmaceutically acceptable salt thereof. Certain embodiments of the present invention are directed to the use of CXCR4 inhibitors that, when administered to a subject, cross the blood-brain barrier (BBB) ​​and enter the brain and central nervous system (CNS). JPEG2026502774000083.jpg3135

Embodiments of the present invention disclose a genetically modified cell that accelerates tissue repair by overexpressing CXCR4. This motile cell can be administered to subjects in need, enhancing tissue regeneration compared to unmodified cells. The cell may include various progenitor cell lines and demonstrates low NF-Kb pathway activity, which suppresses catabolic activity and promotes anabolism in inflammatory environments. The invention also encompasses methods of treatment using these cells, compositions containing them, and kits for their delivery.

The invention provides a method for regulating and controlling proliferation and movement of human peripheral blood T cells by Amuc1100 protein. The method relates to the technologies of separation, activation and culture of human peripheral blood T cells, CCK-8 cell proliferation detection, Transwell cell chemotactic detection, flow cytometry receptor expression body detection and the like. The application of the Amuc1100 protein to treat T cells proves that the protein can significantly down-regulate the expression of CD25 and CXCR4 of the T cells and inhibit T cell proliferation and CXCL12 induced T cell chemotactic movement respectively. The method and research means for in-vitro regulation of T cell proliferation and chemotactic movement can be applied to targeted regulation of T cells and directional migration of intestinal tracts of the T cells, and are used for maintaining the steady state of the intestinal tracts, relieving intestinal inflammations and screening drugs to treat diseases related to the intestinal inflammations.

The invention discloses a double-gene engineered mesenchymal stem cell and application thereof, and relates to the technical field of biological medicines. According to the double-gene engineered mesenchymal stem cell provided by the invention, CXCR4 and TNFSF14 proteins are co-expressed by the mesenchymal stem cell, and the mesenchymal stem cell shows enhanced tumor tropism and immune-mediated anti-tumor activity. Specifically, based on the principles that CXCR4 can enhance the active homing ability of mesenchymal stem cells to gastric cancer lesions expressing ligands SDF-1 (SDF-1 / CXCL12) of the mesenchymal stem cells, TNFSF14 (LIGHT can interact with HVEM and LT betaR receptors to promote activation of T cells and NK cells and the like, the mesenchymal stem cells co-expressing CXCR4 and LIGHT overcome the defects that natural MSCs are insufficient in targeting ability and weak in immune activation ability; the excellent anti-tumor effect is realized.

The application belongs to the technical field of biological medicine, and relates to application of a CXCL14 inhibitor in preparation of a drug for preventing or treating abdominal aortic aneurysm of a patient. The inhibitor effectively eliminates the gender difference of abdominal aortic aneurysm by specifically blocking the combination of CXCL14 and its receptor CXCR4, significantly reduces aortic macrophage infiltration and PDGFRA + macrophage accumulation in the progress of abdominal aortic aneurysm, reduces the degree of collagen degradation and elastic fiber damage, and thus inhibits the pathological progress of abdominal aortic aneurysm. The application provides a new target and drug combination for precise treatment of male abdominal aortic aneurysm, and has clear clinical application value.

Provided are a bionic drug-loaded nanoparticle with expressed CXCR4, a method for preparing same, and use thereof. The method comprises: mixing a lactic acid-glycolic acid copolymer and an immunosuppressant in a certain ratio, and preparing the mixture into a drug-loaded nanoparticle using a microfluidic technology; preparing an MSC cell stably expressing membrane protein CXCR4 and lysing same to extract the cell membrane, so as to give an engineered stem cell membrane; and fusing the engineered stem cell membrane with the drug-loaded nanoparticle to give a bionic drug-loaded nanoparticle with expressed CXCR4. The bionic drug-loaded nanoparticle with expressed CXCR4 is a bionic cell membrane drug-loaded nanoparticle with chemotaxis functionality. By means of genetic engineering, the engineered stem cell membrane is modified to encapsulate a therapeutic agent, and directionally migrates to the lesions in the body and targets specific cells, thereby improving the drug distribution in vivo and reducing adverse effects of immunosuppressants.

The invention discloses an optogenetics system for promoting targeted homing of MSC (mesenchymal stem cells) to damaged liver and a preparation method of the optogenetics system, and develops light-controlled CXCR4 release plasmids containing Uvr8 and Cxcr4 sequences and up-conversion nanoparticles capable of converting NIR (non-infrared radiation) with strong tissue penetrating power into UVB on the basis of the characteristics that UVR8 presents a dimer structure in a natural state and is dissociated after being irradiated by UVB (ultraviolet B). The method is used for realizing overexpression of CXCR4 only on an MSC cell membrane in a liver region so as to promote the targeted homing effect, and can effectively overcome the defects of high carcinogenic risk, complicated operation, low cost benefit and the like in the existing method.

The application discloses double-gene engineered mesenchymal stem cells and application thereof, relates to the technical field of biological medicine. The double-gene engineered mesenchymal stem cells provided by the application co-express CXCR4 and TNFSF14 proteins, exhibit enhanced tumor tropism and immune-mediated anti-tumor activity. Specifically, based on the principle that CXCR4 can enhance the active homing ability of mesenchymal stem cells to gastric cancer lesions expressing its ligand SDF-1 (SDF-1 / CXCL12), and TNFSF14 (LIGHT) can interact with HVEM and LTbetaR receptors to promote the activation of T cells and NK cells, the mesenchymal stem cells co-expressing CXCR4 and LIGHT overcome the defects of insufficient targeting of natural MSCs and weak immune activation ability, and have excellent anti-tumor effect.

The application belongs to the technical field of biological medicine, and provides a CXCR4 high expression type iPSC-NK cell with enhanced bone marrow and tumor tissue homing ability, and a preparation method and application thereof. The cell takes pluripotent stem cells as starting cells, overexpresses a membrane-bound IL-15 and IL-15RA fusion protein gene and a CXCR4 receptor gene in the pluripotent stem cells; pluripotent stem cells stably expressing the target gene are obtained, and then iPSC-NK cells are obtained through induction differentiation. The membrane-bound IL-15 and IL-15RA fusion protein gene and the CXCR4 receptor gene are targetedly integrated into a safe harbor site of the induced pluripotent stem cell through a gene editing technology, so as to construct an iPSC cell strain stably expressing key proteins; the function-enhanced iNK cell is obtained through induction differentiation, and exhibits excellent bone marrow and various solid tumor tissue homing ability and persistent immune killing activity.

The present invention relates to a cell population of spiral ganglion neural progenitors (SGNPs) and methods how to isolate these cells from an in-vitro mixed cell population. The cell population expresses one or more markers, wherein the one or more marker is CXCR4, SUSD2, LPAR3, EPHA5, CHRNA3, REEP1, NPFFR2, SORCS3, NFASC, GABRB3, KCNB2, GRM8, DLL3, and / or KCNH8.

The invention discloses a traditional Chinese medicine composition for treating sarcopenia by regulating a CXCR4 / GPX4 axis to inhibit ferroptosis and a preparation method and application thereof, and belongs to the technical field of traditional Chinese medicines. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 5-15 parts of eucommia ulmoides, 5-15 parts of herba epimedii, 5-15 parts of fructus psoraleae and 5-15 parts of semen cuscutae. The traditional Chinese medicine composition disclosed by the invention has the traditional effects of tonifying kidney, strengthening yang and strengthening tendons and bones, and is proved to be capable of promoting GPX4 expression and inhibiting ferroptosis of muscle cells by up-regulating CXCR4 expression, so that muscle strength is effectively enhanced, proliferation and differentiation of muscle satellite cells are promoted, oxidative stress is reduced, and the traditional Chinese medicine composition is used for preventing or treating sarcopenia.

Normal hematopoiesis relies on a dynamic, interactive network of stromal cell types that secrete a variety of growth factors and cytokines. Two of the most intensely studied molecules implicated in the interaction between HSPCs and stromal cells is the CXCL12 / CXCR4 signaling pair. Mutations resulting in impaired desensitization and enhanced CXCR4 signaling have been identified in the WHIM Syndrome (WS). Hereby, we use a mouse model harboring a WS-linked Cxcr4 gain-of-function mutation (CXCR4 C1013G ), along with a unique and robust co-culture model between primary MSCs and lymphoid-primed MPP (or MPP4). We report functional alterations in MSCs lacking Cxcr4 desensitization, affecting their interaction with MPP4 and interfering with their lymphoid / myeloid specification. In addition, using a human MSC cell line transduced with another WS-linked CXCR4 gain-of-function mutation (CXCR4 R334X ), we show that these genetically engineered MSCs also promoted the myeloid differentiation of human primary HSPCs.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

This invention belongs to the field of protein engineering and biomedicine, and particularly relates to a water-soluble membrane protein, a recombinant vector, a recombinant host bacterium, and their modification methods and applications. The method involves the following steps: First, an interface mutant is constructed based on the SQTY code, and its water solubility and ligand binding ability are evaluated. If the requirements are not met, multiple low-impact transmembrane regions are screened, and after mutation modification, the interface mutant is introduced to construct a single-transmembrane combined mutant, whose water solubility and ligand binding ability are evaluated. If the requirements are still not met, the multiple low-impact transmembrane regions are combined in pairs, and the interface mutant is introduced to construct various double-transmembrane combined mutants, whose water solubility and ligand binding ability are evaluated, and the optimal double-transmembrane combined mutant is selected. This method rationally mutates CXCR4 in stages to achieve water solubility, minimizing changes to the protein's structure and other physicochemical properties, thereby maintaining or even enhancing its binding ability to the ligand CXCL12.

The invention discloses a CXCR4 targeted nuclide diagnosis and treatment integrated probe as well as a preparation method and application thereof, idoCPCR4 is taken as a core targeting structure, a linker L1 containing positive charges is introduced between a bifunctional chelating agent and the idoCPCR4, a novel CXCR4 targeted ligand is prepared, and then a radiolabeled complex is prepared by labeling nuclide. Experimental results show that the affinity of the novel ligand to CXCR4 is remarkably enhanced, and the novel ligand is expected to be applied to CXCR4 targeted nuclide diagnosis and treatment.

The invention provides a Motixazotide-nitrogen mustard conjugate and a preparation method and application of a fluorescent probe of the Motixazotide-nitrogen mustard conjugate, and belongs to the field of polypeptide preparation and biological medicine. According to the present invention, a solid phase polypeptide synthesis method is adopted to covalently link a DNA alkylation reagent nitrogen mustard and a CXCR4 targeting peptide Motixazotide, and further couple with a fluorescent dye so as to successfully prepare a series of novel conjugates and fluorescent probes thereof; experiments prove that the Motixazotide-nitrogen mustard conjugate and the fluorescent probe thereof prepared by the invention can be used for remarkably improving the anti-tumor activity of nitrogen mustard and the targeting property of the nitrogen mustard to tumor cells. Meanwhile, the rhodamine B labeled dinitrogen mustard conjugate BCCR has a specific targeting effect on a CXCR4 receptor and a dual targeting effect on a tumor cell nucleus. The conjugate realizes real-time tracing of the whole process of tumor targeting, cell delivery and nuclear localization, and provides a powerful tool for curative effect evaluation and mechanism research, so that the conjugate has good clinical transformation prospect and application value.

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 present invention relates to compounds and methods useful for dual inhibition of C-X-C receptor type 4 (CXCR4) and Bruton's tyrosine kinase (BTK). The invention also provides pharmaceutically acceptable compositions comprising compounds of the present invention and methods of using said compositions in the treatment of various disorders.

The invention relates to a bifunctional fusion protein targeting CCR5 and gp41 and application of the bifunctional fusion protein in preparation of drugs for resisting human immunodeficiency viruses, and belongs to the technical field of biological medicines. The invention provides a bifunctional fusion protein simultaneously targeting CCR5 and gp41. The bifunctional fusion protein comprises: a fusion protein obtained by connecting a polypeptide 2P23 to an N end and / or a C end of a light chain and / or a heavy chain of an antibody PRO 140 or a PRO 140 mutant through a connecting peptide; or the fusion protein is obtained by connecting a label to the N end and / or the C end of the fusion protein. The novel bifunctional fusion protein constructed by the invention not only overcomes the limitation that a PRO 140 prototype antibody is ineffective to a CXCR4 trophile strain, but also significantly improves the inhibitory activity and broad spectrum to a CCR5 trophile strain, and also has a higher drug resistance barrier.

The present invention belongs to the field of medicine, and particularly relates to a CXCR4-targeting polypeptide and its application. The present invention first provides a CXCR4-targeting polypeptide, which is selected from any one of SEQ ID NO.1-10; then provides a molecular probe, which is composed of a fluorescent label or a radionuclide conjugated to the above-mentioned CXCR4-targeting polypeptide; finally, it also provides the use of any one of the above-mentioned CXCR4-targeting polypeptides and any one of the above-mentioned molecular probes in the preparation of reagents for cancer diagnosis or treatment. The CXCR4-targeting polypeptide provided by the present invention can specifically target CXCR4, conjugate with a fluorescent label or a radionuclide, and achieve high-sensitivity in vivo imaging of tumors; it can be used for tumor screening and early diagnosis, and can also realize the treatment monitoring of tumors. The polypeptide of the present invention has good biocompatibility and safety. The polypeptides of the present invention are all reported for the first time, and are easy to obtain and convenient to promote.

The novel CXCR4 antagonist designed by the invention is composed of a novel CXCR4 antagonist 1, a novel CXCR4 antagonist 2 and a novel CXCR4 antagonist 3, which can be used in combination or independently, the three newly designed CXCR4 antagonists form a molecular architecture different from the existing CXCR4 antagonist, the three structural designs are the basis for realizing high affinity and specific antagonism on CXCR4, and the novel CXCR4 antagonist can be used as a novel CXCR4 antagonist. According to the present invention, the combination of the CXCR4 and the ligand thereof is highly specifically blocked, the activation of the downstream signal channel is effectively inhibited, and compared with the existing clinical use drugs, the significant advantages of the antagonistic activity, the synthesis difficulty and the safety are provided, and the key embodiment of the core treatment value is provided.

The present invention discloses a reagent and application for inhibiting CXCR4 gene expression, belonging to the field of biomedicine technology. The present invention provides an application of a reagent for inhibiting or knocking down CXCR4 gene expression in the preparation of a preparation for preventing and / or treating AFB1-induced cellular inflammation. The present invention uses a siRNA that can effectively inhibit CXCR4 gene expression, and regulates the damaging effect of AFB1 on mouse renal podocytes MPC-5 by affecting the function of the CXCR4 gene and the expression level of downstream signaling pathway genes, which helps to further clarify the molecular mechanism and regulatory mechanism of AFB1-induced glomerular podocyte inflammation, and is of great significance for the development of therapeutic drugs for AFB1-induced glomerular podocyte inflammation.

The invention relates to the technical field of biology, in particular to a method for modular assembly of artery blood vessel type organs and construction of tissue microcirculation of the artery blood vessel type organs. The method comprises the following steps: inducing human pluripotent stem cells to differentiate through a mesoderm stage to form an arterial specific vascular organoid module (AVO), and then carrying out modular assembly on the AVO in vivo or in vitro so as to quickly reconstruct a tissue microcirculation network with arterial characteristics. The obtained artery blood vessel organoid is uniform in form, the diameter of the artery blood vessel organoid is intensively distributed at about 200 microns, SOX17 and CXCR4 artery endothelial markers are expressed at the same time, and the artery blood vessel organoid has polarity and a complete basilar membrane. Transplanting experiments show that the organ can be integrated with host blood vessels in a short time, and ischemic tissue blood perfusion is recovered. The defects that existing organoid is irregular, difficult to splice, delayed in perfusion and the like are overcome, and a new strategy is provided for revascularization and acute ischemic disease repair.

The present invention discloses a class of CXCR4 / HDAC dual inhibitors, their preparation methods, and applications. These dual CXCR4 / HDAC inhibitors are compounds having the structures represented by formula (I) or (II) and / or pharmaceutically acceptable salts thereof: #imgabs0# In formulas (I) and (II): R1 is selected from #imgabs1, R2 is selected from #imgabs2, and L is empty or a saturated or unsaturated aliphatic hydrocarbon chain with a C1-C6 range, preferably a C1-C4 range. These dual CXCR4 / HDAC inhibitors exhibit both CXCR4 antagonism and HDAC inhibition, and are multi-target derivatives that can synergistically achieve anti-tumor, anti-inflammatory, and anti-depressant effects.

The present application discloses a kind of compound for targeting CXCR4 and purposes thereof.The compound is shown in structure of formula (I) or its isotopic variant, hydrate, ester or solvate, tautomer, stereoisomer or pharmaceutically acceptable salt.The compound of the present application connects ligand group (Ra and Rb) for targeting CXCR4 and chelating group Z by linker (L1-X-L2), which has good CXCR4 targeting and specificity, can be quickly imaged in a short time after administration, and can be used for diagnosing and treating CXCR4 overexpression diseases.