33 results about "Hypoxia response" patented technology

The invention relates to a hypoxia response polymer nanoparticle and application thereof. The method comprises the following steps: firstly crosslinking 4,4-diaminoazobenzene and terephthalaldehyde taken as monomers, so as to form a conjugated polymer link, loading a photosensitizer and chemotherapy drugs through noncovalent interaction, and then forming the hypoxia response polymer nanoparticle through a nanoprecipitation method. The hypoxia response polymer nanoparticle can successfully carry the photosensitizer and the chemotherapy drugs to tumor cells, and produce active oxygen during illumination, so as to realize tumor killing. Azo bonds contained in the nanoparticle can be degraded under the action of reductase in cells, and chemotherapy drug release is realized. In addition, cell hypoxia caused during a photodynamic therapy process can further improve drug release, and the hypoxia response polymer nanoparticle can properly realize excellent tumor therapy effect through combination therapy effect of photodynamic therapy and chemical therapy.

Methods are provided for interfering with a hypoxia-mediated transcriptional pathway using an agent that binds to a hypoxia response element and inhibits transcription of a hypoxia inducible gene associated therewith. Also provided are methods of treating a patient with a solid tumors, and compositions useful for treating a patient having solid tumors, including, for example, by administering an agent that binds to a hypoxia response element in a cell. Agents for the methods of the invention are provided including compositions comprising a pyrrole imidazole polyamide or a pharmaceutically acceptable salt or complex thereof.

The invention discloses a hypoxia response lipidosome drug carrier. The hypoxia response lipidosome drug carrier is prepared from phospholipid, cholesterol and hypoxia response molecules, wherein the mass ratio of the cholesterol to the phospholipid ranges from 1:10 to 1:2, and the mass ratio of the hypoxia response molecules to the phospholipid ranges from 1:10 to 1:4; the phospholipid is a mixture of dipalmitoyl phosphatidylcholine, dimyristoyl phosphatidylcholine and methoxy-polyethylene glycol-distearoyl phosphoethanolamine; the hypoxia response molecules are derivatives of a hydrophobic aromatic nitro compound and are located between bimolecular layers of the phospholipid. The hypoxia response lipidosome drug carrier disclosed by the invention is used for loading an antitumor drug, and has a remarkable effect in application to drugs for treating tumors or other hypoxia-related diseases.

The invention discloses a nanoparticle releasing H2S under a hypoxic condition as well as a preparation method and application of the nanoparticle. The nanoparticle has uniform size, good stability and good dispersity in water. The nanoparticle contains a water-soluble H2S donor, a conjugated polymer with a hypoxia response effect, an aza-BODIPY dye with a photothermal effect and a coating material coating the three materials to form the nanoparticle. The nanoparticle has uniform size and good dispersity in water, can release the H2S in the hypoxic environment and solves the problems of poor solubility, low release rate of a traditional H2S donor and the like, so that the H2S has wider application in biological diagnosis and treatment of diseases.

The invention belongs to the technical field of nano-medicaments, and discloses a hypoxia response chiral medicament micelle for targeting triple-negative breast cancer and a preparation method of thehypoxia response chiral medicament micelle. The preparation method comprises the following steps: firstly, introducing an azobenzene group into a molecular chain of carboxyl polyethylene glycol active ester, and obtaining carboxyl polyethylene glycol azobenzene; then, preparing the carboxyl polyethylene glycol-azobenzene-dextrorotatory polylactic acid segmented copolymer through reaction with carboxyl dextrorotatory polylactic acid; then introducing an amino-modified aptamer AS1411 to prepare AS1411-modified polyethylene glycol-azobenzene-dextral polylactic acid, compounding a fat-soluble anti-cancer drug, and then dialyzing to obtain the micelle disclosed by the invention. The low-oxygen-response chiral medicament micelle provided by the invention is small in particle size and narrow indistribution, and can be effectively retained at a targeted part; low-oxygen responsiveness is achieved, and the effect of low-oxygen slow release is achieved; TNBC tumors can be targeted, anti-cancerdrugs are selectively released, and the anti-tumor effect is remarkably improved.

The invention discloses a chromatin peptide. The chromatin peptide substantially is peptide oligomers formed by degradation of a transcription factor of a hypoxic response element in a human body cell anoxic reaction and biological bionic molecules of the peptide oligomers. The transcription factor of the hypoxic response element in malignant tumor cells starts anaerobic respiration in cells, cell proliferation, blood vessel formation and inflammations, and provides energy and space for further expansion of cancer cells. The chromatin peptide generated by the degradation of the transcription factors and the bionic molecules of the chromatin peptide can specifically stop the cell hypoxic response in order to inhibit energy obtaining approaches of the malignant tumor cells, so the malignant tumor cells can naturally grow old toward death in order to realize the treatment purpose.

The invention discloses a urine detection method of platinum super-nanoparticles based on hypoxia response and application of the urine detection method. The platinum super-nano particle PNCA is formed by covalently connecting an aminated super-small platinum nano-cluster and 4, 4 '-dicarboxylic acid azobenzene azo with hypoxia response through an EDC/NHS reaction, and after the surface of the platinum super-nano particle PNCA is coated with a layer of hyaluronic acid HA, the nano particle can specifically target a tumor site. Afterwards, under the action of reductase in the hypoxic environment at the tumor site, the PNCA nanoparticles can be reduced and degraded into many small PtNCs to enter blood circulation again, and the PNCA nanoparticles can be excreted into urine from the kidney for disease state detection due to the fact that the particle size of the PNCA nanoparticles is smaller than the critical value 5.5 nm capable of being removed by the kidney. Due to the excellent hypoxia response effect of the PNCA nanoparticles and the efficient kidney clearing effect of the PtNCs, the PNCA/PtNCs composite material has obvious advantages in living body application.

The invention provides an anti-hypoxia and anti-fatigue food, health-care product or pharmaceutical composition, and a preparation method and application thereof. The composition is a food, health-care product or pharmaceutical preparation prepared from the following raw materials in parts by weight: 24-36 parts of ginseng, 80-120 parts of rhizoma polygonati, 16-24 parts of cordyceps militaris, 16-24 parts of albumin peptide, 16-24 parts of spirulina maxima, 16-24 parts of chia seeds, 16-24 parts of fructus lycii, 16-24 parts of sea buckthorn and 0.1-1 part of vitamin C. The composition disclosed by the invention is reasonable in compatibility, and plays a synergistic effect on fatigue resistance and oxidation resistance; the composition can also be used for relieving altitude stress and preventing acute and chronic altitude hypoxia diseases; meanwhile, the raw materials used in the composition disclosed by the invention are safe and free of toxic and side effects; safe and efficient energy supply can be provided; the endurance capacity of an organism to an anoxic environment is enhanced; symptoms, such as an anoxic reaction of the organism, are effectively relieved; and the composition has a good application prospect.

The invention provides a nitroimidazole derivative for preparing a hypoxic developer. The nitroimidazole derivative is selected from compounds with structural formulas as shown in a formula I, a formula II or a formula III, wherein R is C1-8 alkyl, saturated alkoxy or acylamino. The invention also provides a preparation method of the nitroimidazole compound and application of the nitroimidazole compound in preparation of a PET imaging agent. The nitroimidazole derivative provided by the invention has proper molecular weight and fat solubility, greatly improves the ability of an imaging agent to cross a blood brain barrier, and has higher sensitivity to hypoxia due to introduction of an azide hypoxia response group.

The invention relates to a co-assembly system based on extracellular vesicles and used for hypoxia response imaging. The co-assembly system comprises the extracellular vesicles and Pc/C5A attached to the extracellular vesicles, and the Pc/C5A contains calixarene QAC5A-6C and aluminum phthalocyanine AlPcS4. The method comprises the following steps: mixing calixarene QAC5A-6C (C5A) and aluminum phthalocyanine AlPcS4 (Pc), and carrying out first incubation to obtain Pc/C5A; and mixing with extracellular vesicles, and carrying out second incubation, so as to obtain the co-assembly system for hypoxia response imaging.

The present invention relates to therapeutic agents, particularly to therapeutic polypeptides and nucleic acids having the capacity for selective expression under conditions of hypoxia, cells incorporating the nucleic acids and their use in therapy, in particular in methods requiring selective expression under conditions of hypoxia, such as typically found in solid cancers. The nucleic acids encode novel hypoxia-responsive chimeric antigen receptors (CARs). The invention also relates to hypoxia-responsive regulatory nucleic acids.

The invention provides a preparation method of an angelica polysaccharide derivative for sensitizing ferroptosis through hypoxia response. The preparation method comprises the following steps: S1, carrying out synthesis of a carrier material: firstly, synthesizing angelica polysaccharide-azobenzoic acid, then synthesizing angelica polysaccharide-azobenzoic acid-ferrocene methanol, and finally, forming arachidonic acid-angelica polysaccharide-azobenzoic acid-ferrocene methanol; and S2, carrying out dialysis and freeze-drying treatment on the carrier material. According to the preparation method disclosed by the invention, by introduction of exogenous iron ferrocene, introduction of a ferroptosis precursor arachidonic acid and consumption of NADPH, which is caused by azobenzene bond degradation, ferroptosis is selectively sensitized, and cancer cell death is synergistically promoted. Reduction of azobenzene bonds involved in the preparation method disclosed by the invention causes a failure of the tumor NADPH, so that the concentration of intracellular GSH and Trx is reduced, the concentration of intracellular ROS is increased, and tumor cell ferroptosis is indirectly promoted. Based on liver targeting and passive targeting of angelica polysaccharide, the preparation method fulfills the aim of accurate tumor targeting drug delivery of the derivative.

The invention provides an anti-hypoxia food, health-care product or pharmaceutical composition, and a preparation method and application thereof. The composition is a food, health-care product or pharmaceutical preparation prepared from the following raw materials in parts by weight: 80-120 parts of rhizoma polygonati, 24-36 parts of ginseng, 16-24 parts of cordyceps militaris, 16-24 parts of spirulina maxima, 16-24 parts of chia seeds, 16-24 parts of fructus lycii, 16-24 parts of albumin peptide, 16-24 parts of oyster peptide, 16-24 parts of sea buckthorn, 12-18 parts of pollen pini and 0.1-1 part of vitamin C. The composition disclosed by the invention is reasonable in compatibility, and plays a synergistic effect on fatigue resistance and oxidation resistance; the composition can also be used for relieving altitude stress and preventing acute and chronic altitude hypoxia diseases; meanwhile, the raw materials used in the composition are safe and free of toxic and side effects; safe and efficient energy supply can be provided; the endurance capacity of an organism to an anoxic environment is enhanced; symptoms, such as an anoxic reaction of the organism, are effectively relieved; and the composition has a good application prospect.

The invention provides an intracellular polymerization method for hypoxia response type alkyne-amine click polymerization and application of the intracellular polymerization method, and belongs to the technical field of biochemistry. The intracellular polymerization method for hypoxia response type alkyne-amine click polymerization, provided by the invention, comprises the following steps: (1) performing hypoxia culture on cells in a binary nitro compound solution; (2) transferring the cells subjected to hypoxic culture in the step (1) into a binary alkynyl compound solution for normal oxygen culture; and (3) transferring the cells subjected to the normal oxygen culture in the step (2) into a culture medium for normal oxygen culture, so as to realize intracellular polymerization of hypoxia response type alkyne-amine click polymerization. The binary nitro compound is reduced into a diamine compound through nitroreductase in a cell under the hypoxic condition, and the reduced diamine compound and a binary alkynyl compound are polymerized in the cell, so that anchoring of fluorescent small molecules is realized, a fluorescent signal is lightened, and fluorescence imaging of the cell is realized.

The invention discloses a gene editing method for hypoxia response. The nanometer composite material APACP is composed of Cas9/sgRNA and AuNRs modified by p-carboxyl azobenzene, and the outermost layer of the nanometer composite material APACP is wrapped with a layer of polyethyleneimine PEI. According to the present invention, 4-carboxylazobenzene is subjected to specific reduction in the tumor hypoxic microenvironment, such that the azo bond is broken, such that the accurate and controllable release of Cas9/sgRNA covalently linked to the APACP nano-particle is achieved, and the effective gene editing is achieved based on the CRISPR-Cas9 system; according to the photo-thermal conversion characteristic of AuNRs, after a target gene in tumor tissue is knocked out in Cas9/sgHSP90, a photo-thermal therapy is used for treating tumors. Cell and animal experiments prove that the treatment method is effective and superior to AuNRs photo-thermal treatment, and the wide potential of the APACP nanoparticles in tumor treatment is also proved.

The invention discloses a two-stage integrated biological nitrogen and phosphorus removal reactor. The reactor comprises a reactor main body. The inner chamber of the reactor main body is divided into a primary reaction zone and a secondary reaction zone through a secondary reactor in the inner chamber. The primary reaction zone is orderly divided into an anaerobic sludge discharge unit, an anaerobic reaction unit and an overflow unit from bottom to top along the axial direction of the reactor main body. The secondary reaction zone is orderly divided into an anoxic denitrification unit, a three-phase separation unit and an aerobic biofilm reaction unit from bottom to top along the axial direction of the reactor main body. A return device is arranged outside the reactor main body. The aerobic biofilm reaction unit is communicated with an anoxic reaction digestion unit through the return device. The two-stage integrated biological nitrogen and phosphorus removal reactor creates aerobic, anoxic and anaerobic alternating environments, keeps a high COD removal rate and realizes simultaneous removal of nitrogen and phosphorus. The integrated reactor saves a floor space. Residual sludge and phosphorus-rich sludge in the aerobic reaction zone can be smoothly discharged. The acid production reaction in the anaerobic reaction unit can provide acidity for the anoxic reaction unit.

The invention discloses a polymer micelle material, preparation and application thereof, and a targeted drug of the polymer micelle material, preparation and application thereof, wherein the polymer micelle material has a chemical formula as shown in a formula (1). According to the invention, the polymer micelle material is grafted with a nitroimidazole hypoxia response group on a side chain, and surface glucose target molecule modification is further carried out in some specific embodiments, so that the polymer micelle material not only has the performance of actively targeting tumors, but also has hypoxic microenvironment response, can release drugs in a hypoxic microenvironment, and realizes efficient drug delivery and tumor treatment.

The invention belongs to the field of biological analysis, particularly relates to a synthesis method and application of a hypoxia response type ratio probe, and aims to solve the problem that the hypoxia degree cannot be accurately and reliably evaluated since only qualitative hypoxia detection can be realized in the conventional hypoxia imaging of a living body. The synthesis method comprises the following steps: modifying a fifth generation of polyamide-amine dendrimer PAMAMG5 by adopting an anthocyanin fluorescent dye Cy5-NHS to obtain PG5-Cy5; encapsulating a nitroreductase response type fluorescent molecule Cy7-NO2 in a hydrophobic cavity of PG5-Cy5 to form Cy7-NO2/PG5-Cy5; and modifying the outer layer of the Cy7-NO2/PG5-Cy5 with oligo-hyaluronic acid (LWHA) selected as a tumor recognition group, and synthesizing the Cy7-NO2/PG5-Cy5@LWHA. The hypoxia response type ratio probe prepared by the invention has the characteristics of high sensitivity, high specificity and long in-vivo circulation.