23 results about "Tumor vascularity" patented technology

The present invention provides novel Compound (1) having tumor vascular remodeling effect and / or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, and medical uses thereof.

The invention discloses a multi-target self-assembly cyclic peptide with tumor microenvironment regulation and control, belongs to the technical field of nano medicine, and aims to solve the problems of short blood vessel normalization period, inconsistent action time of combined medicines and the like in a traditional clinical combined treatment scheme. The self-assembly cyclic peptide comprises a TIGIT blocking unit, a self-assembly unit and a blood vessel regulation and control targeting unit which are connected in sequence, the blood vessel regulation and control targeting unit comprises a Tie2-VEGF targeting fragment and a corner structure fragment, and the Tie2 targeting fragment, the VEGF targeting fragment and the corner structure fragment are coupled through disulfide bonds to form an annular peptide. The synthesized multi-target self-assembly cyclopeptide can be quickly self-assembled to form a nanofiber network with a beta-folding structure after being enriched at a tumor site, and the nano reticular supramolecular assembly structure has the effects of strong combination and long-acting retention at a target protein, so that the functions of long-acting blocking and regulation and control of tumor blood vessels and immune microenvironment are achieved.

The invention relates to lipid nanoparticles and application thereof. The invention relates to a lipid nanoparticle, which is prepared from a cationic lipid, an anionic lipid DOPS (1, 2-dioleoyl-sn-glycerol-3-phosphatidyl-L-serine), other lipids and a targeting antibody. Research finds that the transfection efficiency of the nanoparticles on spleen T cells can be remarkably improved by doping anion lipid DOPS and indirectly coupling a targeting antibody. According to the invention, nucleic acid encoding CAR protein targeting tumor vascular endothelial cells and tumor cells is further loaded in the lipid nanoparticles and is used for tumor treatment, which results in that the treatment significantly promotes intra-tumor infiltration of immune cells and significantly inhibits progression of various solid tumors; a new thought and a new means are provided for effective application of the CAR-T therapy in solid tumors.

The application discloses a kind of lipid nano-drug delivery system and its preparation method in the application of improving tumor vascular normalization, the lipid nano-drug delivery system includes drug, CaO2 Nanoparticle and anionic liposome, the drug and CaO2 Nanoparticle are co-loaded in the anionic liposome;The surface of the CaO2 Nanoparticle is with positive charge, and the preparation raw material of the anionic liposome contains 1,2-dioleoyl-sn-glycerol-3-phosphoric acid sodium salt. 2+ The lipid nano-drug delivery system can enhance endothelial cell-derived NO production by mediating eNOS activation of Met and other drugs and Ca

The present invention discloses engineered platelets carrying platelet activation inhibitor nanoparticles, a preparation method and application thereof, which belongs to the field of pharmaceutical technology and relates to a preparation method of engineered platelets carrying ticagrelor nanoparticles and its therapeutic use in malignant solid tumors. The preparation of the engineered platelets described in the present invention includes the steps of extracting and purifying platelets, preparing gelatin nanoparticles loaded with platelet activation inhibitors, anchoring the nanoparticles to the outer surface of platelets, etc. The engineered platelets of the present invention are targeted to reach the tumor site by recruiting tumor-associated platelets in the body, and specifically respond to matrix metalloproteinases to release the carried platelet activation inhibitor, thereby inhibiting the activation of platelets in the tumor microenvironment, enhancing tumor vascular leakage, alleviating the immunosuppressive microenvironment, and effectively enhancing the effects of chemotherapy and immunotherapy.

This invention belongs to the field of ultrasound contrast microbubble synthesis technology, and relates to a method for preparing and applying ultrasound contrast microbubbles targeting CD93 molecules in tumor vascular endothelium. The method includes the following steps: constructing a recombinant expression vector capable of expressing the CD93 ligand MMRN2 protein, transfecting cells, and extracting the cell membrane using differential centrifugation; mixing dipalmitoylphosphatidylcholine, distearate phosphatidylethanolamine-polyethylene glycol 2000, and chloroform, adding DiI, and preparing a liposome membrane using a thin-film hydration method; mixing the cell membrane and the liposome membrane, performing ice-bath sonication, and mixing and shaking with perfluoropropane to obtain an ultrasound contrast agent targeting CD93 molecules in tumor vascular endothelium. The ultrasound contrast microbubbles prepared by the method of this invention have good biocompatibility compared to conventional antibody-targeting strategies, and can also improve stability and targeting, thereby enabling the assessment of CD93 molecule expression in tumors.

FIELD: oncology.SUBSTANCE: used to treat malignant embryonic tumors. The method involves pharmacological inhibition of factors that support tumor growth. A progesterone receptor antagonist is administered and immunological activation of the body's response against progesterone-induced blocking factor (PIBF), placental growth factor (PIGF) and trophoblastic β 1-glycoprotein.EFFECT: increased treatment reliability due to a comprehensive and selective effect on the tumor, simultaneous influence on both the primary tumor site and metastases, a reduction in the likelihood of relapse due to the destruction of the tumor vascular network, and a reduction in the overall toxic load on the patient's body during treatment.7 cl, 1 tbl, 5 ex

The application belongs to the technical field of biological medicine, and discloses a polypeptide specifically targeting a vascular marker molecule VEGFR2 and application thereof, wherein the amino acid sequence of the polypeptide is as follows: i) an amino acid sequence as shown in SEQ ID NO. 1; or ii) an amino acid sequence obtained by connecting a label to the N terminal or the C terminal of i); or iii) a functional polypeptide obtained by substituting, deleting and / or adding one or more amino acids in the amino acid sequence of i) or ii). The polypeptide provided by the application can target VEGFR2 positive cells, has high selectivity, and can be used as a target head of a targeted drug to increase the content of the drug in human tumor vascular marker molecule VEGFR2 positive cells. The polypeptide has high targeting property, simple preparation method and low cost, and therefore has good practical application value.

The invention belongs to the technical field of protein polypeptides, and particularly discloses a CD93 affinity peptide and application thereof in preparation of antitumor drugs or detection reagents. The polypeptide with a CD93 protein affinity effect is obtained through repeated screening and optimization, and an affinity blocking activity experiment proves that the CD93 affinity peptide can affine an extracellular IgV-like structural domain of the CD93 protein and block the interaction of CD93 / IGFBP7 protein. An HUVECs cell in-vitro migration experiment and a tube formation experiment verify that the CD93 affinity peptide can inhibit migration of HUVECs cells and tube formation, promote normalization of tumor vascular functions and further inhibit growth of tumors, and has no obvious toxic or side effect. The CD93 affinity peptide provided by the invention can be used for preparing anti-tumor drugs (including anti-tumor immunotherapy drugs) or detection reagents taking CD93 as a target spot, has a better medical application prospect, and provides a new choice for tumor immunotherapy.

The application relates to a kind of lipid nanoparticles and its application.The lipid nanoparticles include: cationic lipid, anionic lipid DOPS (1,2-dioleoyl-sn-glycerol-3-phosphatidyl-L-serine), other lipids and targeting antibody.The application finds that doping anionic lipid DOPS and indirectly coupling targeting antibody can significantly improve the transfection efficiency of nanoparticles on spleen T cells.The application further loads nucleic acid encoding CAR protein targeting tumor vascular endothelial cells and tumor cells in the above lipid nanoparticles and is used for tumor treatment, and the results show that the above treatment significantly promotes intratumoral infiltration of immune cells, significantly inhibits the progression of various solid tumors, and provides a new idea and new means for the effective application of CAR-T therapy in solid tumors.

The application provides sulfated derivatives of fucosylated chondroitin sulfate oligosaccharides and application thereof, and belongs to the technical field of marine drugs. The structure of the sulfated derivatives of fucosylated chondroitin sulfate oligosaccharides is mainly a disaccharide repeating unit with GlcA and GalNAc connected through a beta-1,3 / beta-1,4 glycosidic bond as a main chain, and a fucose connected to the O-3 position of GlcA as a side chain; sulfation occurs at any 1-3 positions of C4 and / or C6 of the acetylglucosamine in the main chain, and C2,3,4 of the fucose in the side chain. Through in-vivo and in-vitro level verification, the application plays an anti-tumor metastasis role by significantly inhibiting the adhesion of tumors to endothelium, platelets and the like and tumor angiogenesis, so as to use S-dFCS as an active substance, prepare a medicine or a health product with the aid of a pharmaceutically acceptable carrier, and be capable of being used for preventing and treating tumors and diseases related to postoperative metastasis.

The invention discloses a drug delivery system taking tumor vascular endothelial cells as targets and application of the drug delivery system, and belongs to the technical field of biological medicines. The invention provides a delivery carrier taking a tumor vascular endothelial cell as a target spot. The delivery carrier comprises an exosome and MMRN2 and / or IGFBP7 protein modified at an extracellular domain of an exosome membrane protein. The invention further provides a drug delivery system with tumor vascular endothelial cells as targets, and the drug delivery system comprises the delivery carrier and tumor treatment drugs wrapped in the delivery carrier. The exosome is modified to target CD93 molecules on the surface of glioma vascular endothelial cells, so that the drug is enriched in glioma, the curative effect is enhanced, and the safety is improved; the compound can specifically activate inflammation signal channels in glioma vascular endothelial cells, induce inflammatory response in glioma and remodel tumor-associated macrophages, can directly inhibit tumor growth, can promote presentation of tumor-associated antigens, and induces strong tumor specific immune response.

The application provides a kind of double drug co-loading intelligent liposome and its preparation method and purposes, belong to the field of biological medicine.The double drug co-loading intelligent liposome includes the following raw materials: curcumin, near-infrared type photosensitizer, phospholipid A, sterol compound, polyethylene glycol modified targeting lipid;The polyethylene glycol modified targeting lipid is sequentially connected by phospholipid B, responsive link, polyethylene glycol and tumor targeting ligand.The application constructs double drug co-loading liposome system with active targeting and tumor microenvironment responsiveness, forms the efficient synergistic treatment strategy of "vascular normalization+PDT", realizes drug precise delivery and enrichment, has excellent ability to inhibit tumor growth, induce tumor vascular normalization and relieve tumor hypoxia, has synergistic effect in inhibiting HIF-1 alpha expression, significantly improves the treatment effect, and provides a new scheme for efficient and safe treatment of tumor.

The application discloses an NGR peptide coupled ruthenium complex and a preparation method and application thereof, and belongs to the technical field of tumor photodynamic therapy. The application couples NGR peptide and a two-photon active ruthenium complex to construct a double-targeted photosensitizer. The NGR oligopeptide can specifically combine with CD13 receptors which are highly expressed on the surface of tumor vascular endothelial cells and tumor cells, realize double targeting of'vessel+tumor cell', and significantly improve the tumor enrichment efficiency of drugs. The NGR peptide coupled ruthenium complex provided by the application can efficiently generate active oxygen under the excitation of 820 nm near-infrared light, specifically kill CD13 positive target cells, and the tissue penetration depth can reach 250 microns, which is suitable for deep tumor treatment. Meanwhile, the NGR peptide coupled ruthenium complex can efficiently destroy the pipe forming ability of vascular endothelial cells, and significantly inhibit tumor angiogenesis.

The present application provides a silk fibroin vascular embolism agent loaded with polyhydroxy phenolic compounds, which is prepared from a silk fibroin compound loaded with polyhydroxy phenolic compounds, wherein the silk fibroin compound loaded with polyhydroxy phenolic compounds is prepared by self-assembly of polyhydroxy phenolic compounds and silk fibroin, the silk fibroin is treated by a beta-fold conformation transformation process, and the mass ratio of polyhydroxy phenolic compounds to silk fibroin is <1:1; the vascular embolism agent is prepared by one of emulsification dispersion method, phase separation coagulation method, supercritical fluid technology, electrostatic adsorption method and dry granulation method. The vascular embolism agent has good biocompatibility and degradability, can effectively block blood flow, realize rapid hemostasis, and can be used for tumor vascular embolism treatment. Through the innovative self-assembly strategy, the mechanical properties of the silk fibroin microspheres are significantly improved. Compared with traditional hemostatic materials, the vascular embolism agent exhibits faster settling speed and higher hemostatic efficiency.

The application belongs to the technical field of biological medicine, and particularly relates to design, synthesis and application of a tumor-targeting polypeptide tracer. The structure of the tumor-targeting polypeptide tracer comprises a tumor-targeting polypeptide (targeting vascular endothelial growth factor receptor 2 of tumor cells), a linker and a radionuclide chelating group. The polypeptide tracer provided by the application is modified by methionine at different sites to form a thioether bridge cyclic peptide, so that the tumor targeting ability, membrane penetration performance and in-vivo drug metabolism of the targeting polypeptide are improved, high concentration enrichment and long-time retention in the tumor tissue site can be realized, the targeting of the PET tracer is improved, and a more accurate and safer tumor tracer is realized.

The invention discloses an RGD targeted diagnosis and treatment integrated boron medicine as well as preparation and application thereof. The core innovation lies in that a photoacoustic imaging molecule taking boron-10 isotope as a core is designed, and the molecule has double functions: the molecule is used as a photoacoustic imaging unit to realize visual positioning of tumors, and is also used as a boron-10 unit required by boron neutron capture therapy (BNCT) to realize diagnosis and treatment integration on the molecular level. The core molecule is modified through carboxylation derivation, so that the core molecule can be efficiently connected with RGD tumor targeting peptide through an amido bond, and a targeting diagnosis and treatment conjugate is constructed. The conjugate can specifically recognize an alpha v beta 3 integrin receptor on the surface of a tumor vascular endothelial cell, and the tumor targeting property is remarkably improved. The invention not only provides an innovative drug design platform, but also solves the problem of separation of diagnosis and treatment in traditional BNCT through molecular structure optimization, and provides a reliable technical basis for accurate imaging-guided boron neutron capture therapy.

The invention relates to the technical field of brain glioma organoid construction, in particular to a method for constructing a brain glioma organoid, which comprises the following steps: step S1, mixing a brain glioma sample and primary brain microvascular endothelial cells according to a cell number ratio of 1: 5, inoculating into a porous structure of a stent after mixing, and singly inoculating the primary brain microvascular endothelial cells into a hollow vascular channel of the stent; s2, the stent in the step S1 is placed in a gas-liquid interface culture device to culture a brain glioma sample, the gas-liquid interface culture device comprises a culture medium, the bottom of the stent is immersed in the culture medium, the top of the stent is exposed to a mixed gas environment, and the brain glioma sample is cultured through the design of the composite stent containing the porous proliferation area and the hollow blood vessel channel. The problems of low medicine permeation efficiency and limited tumor-blood vessel interaction research caused by blood vessel deficiency of a traditional model are solved.

The application belongs to the technical field of brain glioma organoids, and particularly relates to a method for constructing brain glioma organoids, which comprises the following steps: S1, mixing a brain glioma sample with primary brain microvascular endothelial cells at a cell quantity ratio of 1:5, and then inoculating the mixture into a porous structure of a scaffold, wherein the hollow vascular channel of the scaffold is inoculated with the primary brain microvascular endothelial cells; and S2, culturing the scaffold in step S1 in a gas-liquid interface culture device to culture the brain glioma sample, wherein the gas-liquid interface culture device comprises a culture medium, the bottom of the scaffold is immersed in the culture medium, and the top of the scaffold is exposed to a mixed gas environment; through the composite scaffold design comprising the porous proliferation area and the hollow vascular channel, the problems of low drug penetration efficiency and limited tumor-vascular interaction research caused by the vascular deficiency of a traditional model are solved.

The invention belongs to the field of developers, and particularly relates to developable particles as well as a preparation method and application thereof. The developable particle provided by the invention is prepared by taking iodine-containing alcohol as a main body through a physical crushing or reversed-phase emulsification cross-linking process, and can be used for directly loading a medicine and developing for a long time. Compared with embolism drug-loading microspheres sold in the market, the drug adsorption capacity of the developable particles is larger than or equal to 140 mg / g within 3 min, the adsorption rate within 1 d is larger than or equal to 90%, the developable particles have the functions of developing, rapid drug loading and controllable release, and the developable particles can be used for preparing tissue gasket drugs, tissue filling drugs, tumor vascular embolism drugs and radiotherapy labeling drugs.

The invention discloses a coagulant-loaded embolism microsphere as well as a preparation method and application thereof, the embolism microsphere is prepared through microfluidic and free radical polymerization technologies, and the coagulant-loaded embolism microsphere has a wide application prospect in the fields of arterial embolism treatment, tumor vascular infarction and the like. The embolism microspheres have the characteristics of uniform size, efficient entrapment and continuous release of the coagulant, and can effectively promote fibrinogen to generate fibrin and accelerate coagulation of rabbit blood. Besides, the thrombin-loaded embolism microspheres can obviously induce tumor artery occlusion, and obvious blood clots are formed in far-end blood vessels, so that the growth of rabbit in-situ VX2 tumors is effectively inhibited. The embolism microsphere carrying the coagulant has the advantages of being high in safety, easy and convenient to prepare, good in embolism effect and the like, and efficient entrapment and controllable release of thrombin can be achieved. In the aspects of liver cancer transarterial embolism and tumor vascular infarction treatment, the technology has great transformation potential and is expected to promote the development of vascular embolism agents.

The invention provides a temperature response type magnetic emulsion embolization agent containing triptolide as well as a preparation method and application of the temperature response type magnetic emulsion embolization agent, and belongs to the technical field of biological medicines. The triptolide temperature response type magnetic emulsion embolization agent comprises triptolide, a temperature-sensitive polymer, iodized oil and magnetic nanoparticles, and the temperature-sensitive polymer can be subjected to phase change at 32 DEG C or above to be gelated. The triptolide temperature response type magnetic emulsion embolism agent provided by the invention can continuously release triptolide and has excellent mechanical properties to realize long-acting tumor vascular embolism, and the magnetic nanoparticles can effectively exert magnetocaloric properties to realize an anti-tumor effect; the iodinated oil has X-ray opaqueness and can be visualized in an embolism operation, the safety in the using process is improved, and then the triple synergistic anti-tumor effect of embolism, chemotherapy and magnetic hyperthermia is achieved.

The present invention provides a novel Compound (1) which has a tumor vascular remodeling effect and / or anti-CAF (Cancer Associated Fibroblasts) activity, or a pharmaceutically acceptable salt thereof, optionally in pharmaceutically acceptable and medical uses thereof. Compound (1)