73 results about "Hypoxic tumor" patented technology

Inositol-tripyrophosphate is an allosteric effector of hemoglobin due to its ability to cross the plasma membrane of red blood cells and deliver oxygen to solid tumors, by lowering the oxygen affinity of the hemoglobin of red blood cells. The present invention is directed to the use of inositol-tripyrophosphate to reduce hemoglobin's affinity for oxygen in circulating red blood cells. The present invention is further directed to the use of inositol-tripyrophosphate to inhibit angiogenesis and enhance radiation sensitivity of hypoxic tumors. The present invention is further directed to the use of inositol-tripyrophosphate for the treatment of various types of cancers, Alzheimer's disease, stroke and osteoporosis.

The present invention provides a composition and method for targeting hypoxic tumor areas for detection or treatment or a treatment adjuvant for cancer. Specifically, a hypoxia targeting moiety is conjugated to a polymeric micelle containing imaging agents, therapeutic agents, or therapeutic adjuvants.

Inositol-tripyrophosphate is an allosteric effector of hemoglobin due to its ability to cross the plasma membrane of red blood cells and deliver oxygen to solid tumors, by lowering the oxygen affinity of the hemoglobin of red blood cells. The present invention is directed to the use of inositol-tripyrophosphate to reduce hemoglobin's affinity for oxygen in circulating red blood cells. The present invention is further directed to the use of inositol-tripyrophosphate to inhibit angiogenesis and enhance radiation sensitivity of hypoxic tumors. The present invention is further directed to the use of inositol-tripyrophosphate to enhance PO₂ in hypoxic tumors.

The invention discloses a nano-prodrug of light-induced self-produced oxygen, singlet oxygen and active divalent platinum for the treatment of hypoxic tumors. The nano-prodrug is a hydrophobic photosensitizer via a hydrophilic linker and Azido-containing tetravalent platinum [Pt(N ₃ ) ₂ (OH)(O ₂ C(CH ₂ ) _n COOH)(Am1) ₂ ] Linked amphiphilic photodynamic-chemotherapy combined anticancer prodrugs, self-assembled into nanoparticles in water, and loaded with up-conversion nanoparticles. The invention decomposes under the light of 980 nanometers to produce oxygen and divalent platinum with anticancer activity, and the oxygen produced by itself can be utilized by the photosensitizer in the prodrug to generate singlet oxygen, and finally singlet oxygen and anticancer activity The combination of active divalent platinum achieves the effect of photodynamic-chemotherapy combined therapy, thereby reversing the resistance of tumor hypoxic areas to photodynamic therapy and improving the therapeutic effect of tumors; at the same time, it is particularly stable in the absence of light and can reduce Toxic side effects on normal cells.

The invention discloses a preparation for enhancing hypoxic tumor photodynamic therapy and a preparation method and application of the preparation, and belongs to the technical field of medicines. The preparation is a nano preparation formed by self-assembly of an active oxygen sensitive material and a photosensitive material, the active oxygen sensitive material is obtained by modifying a hydrophilic polymer material with a phenylboronic acid ester group, and the photosensitive material is obtained by modifying the hydrophilic polymer material with a photosensitizer. The preparation method comprises the following steps that a functional amphiphilic polymer, namely the active oxygen sensitive material and the photosensitive material is constructed, and then drugs capable of inhibiting mitochondrial respiration of cells are encapsulated by a self-assembly method to prepare the preparation. The preparation has good stability in tumor tissues and cells, and can quickly respond to stimulation to release the drugs when being stimulated by external light.

The present invention generally relates to oxazine derivative compounds and related compositions and methods for inducing hypoxic tumor cell death, treating cancer and locating a hypoxic tumor in a subject.

The invention discloses a long-life fluorescein derivative with a hypoxia targeting function as shown in a structural formula I, a synthesis method of the derivative and a biological application of the derivative. In the formula, L is -CH2-O-CH2-, CO-O-CO- or -COO-CH2-, and R is a symmetric C10H8N2O, C8H8O or C6H6OS structure. The long-life fluorescein derivative I can be used for detecting nitroreductase (NTR) in hypoxic tumor tissues. With long triplet-state life, the derivative I can produce a singlet state for photodynamic therapy of hypoxic tumors. The fluorescein derivative based on traditional stains has integrated diagnosis and treatment effects and has the potential of playing a role in biological application.

The invention belongs to the technical field of chemical analysis, and relates to a small molecular fluorescent probe, particularly to a nitroreductase fluorescent probe based on nitro reduction and sulfur-nitrogen transposition, wherein the fluorescent probe is a BODIPY structure nitroreductase fluorescent probe. The invention discloses preparation and applications of the probe and a novel reaction mechanism for nitroreductase recognition. The fluorescent probe disclosed by the invention is stable in photophysical activity and high in nitroreductase response sensitivity, and can be applied tofluorescence imaging detection of hypoxic tumor cells.

The invention discloses a hypoxic activation prodrug based on 2,2-dimethyl-3-(2-nitroimidazolyl) propionic acid. The hypoxic activation prodrug is connected with an antitumor drug by using 2,2-dimethyl-3-(2-nitroimidazolyl) propionic acid by virtue of an ester bond and has a structure shown as a formula I, wherein R1 and R2 include, but are not limited to the following structures: hydrogen, hydroxyl, chlorine, bromine, fluorine, C1-C6 alkyl, C1-C6 alkyl containing alkenyl and C1-C6 alkyl containing alkynyl; and the antitumor drug comprises paclitaxel and docetaxel. The hypoxic activation prodrug has the characteristics that a hypoxic region of a tumor can be targeted, the hypoxic activation prodrug can be reduced by a specific enzyme highly expressed in a hypoxic tumor tissue, and a crude drug is released by a reduced amino imidazolidine acid compound under the action of intramolecular cyclisation. The prodrug provided by the invention is stable in vitro and vivo and capable of releasing a drug by specific reduction in the hypoxic tumor tissue, improving the targeting ability of the antitumor drug, reducing toxic or side effects and improving the curative effect.

The invention provides hydrophilic complexes marked by radioactive nuclide for hypoxic tumors; and the precursor of the complexes is a 1, 4, 8, 11-tetraazacyclotetradecane-contained 2-methyl-5-nitromidazole compound with the structural formula as shown on the right. The invention also provides preparation methods of the complexes and the precursor thereof, and the application of the complexes as potential tumor hypoxia imaging agents; and the complexes have good hydrophilic property and relatively high uptake value in tumors, especially the complexes such as TcO-MNIEC and TcN-MNIEC have high absolute uptake value in tumors, low L/NT value, relatively high tumor/muscle ratio and tumor/blood ratio, effectively solve the problem that the current tumor hypoxia imaging agent has the defects of low absolute uptake value and high L/NT value, thus being likely to become new tumor hypoxia imaging agents with better performance.

Novel phosphate-bearing prodrugs of sulfonyl hydrazines have the formulas I, II, III and IV. Pharmaceutical compositions and uses thereof in the treatment of cancer are claimed. The aforementioned prodrugs include enantiomers, stereoisomers and tautomers thereof, as well as pharmaceutically acceptable salts or solvates and metabolites from all stages. The aforementioned prodrugs are preferentially activated in hypoxic tumors and can be given either alone, or in combination with other anticancer agents or with phototheraphy or radiotherapy.

Where R=C_1-10 alkyl, or C_1-10 haloalkyl (preferably containing no more than 5 halogen groups, preferably 2-chloroethyl);

R′ and R″ are independently C_1-10 alkyl, or C_5-20 aryl or heteroaryl (preferably methyl);

R₁ is H, C_1-10 alkyl, C_1-10 alkoxyl, C_5-20 aryl or heteroaryl or C_5-20 aroxyl or heteroaroxyl (preferably methyl and ethyl);

X is O, NH, or NR (preferably O);

Y is (CH₂)_n, O(CH₂)_n, NH(CH₂)_n, NR(CH₂)_n, OCOO(CH₂)_n, NHCOO(CH₂)_n;

n is 1, 2, 3, 4 or 5 (preferably n=2 and 3); or Y=aryl or heteroaryl (preferably para-phenyl); A=CH, or N (preferably CH); and B=CH═CH, O, S, NH, or NR (preferably CH═CH); or pharmaceutically acceptable salts, solvates, polymorphs or metabolites, thereof.

Therapeutic ureido-sulfonamide compositions having compounds with the formula

R-Q-Ar—SO₂NH₂

are disclosed, which compounds selectively inhibit CAIX and CAXII, and which are effective to inhibit hypoxic tumor growth, suppress metastases, and impair and deplete cancer stem cells in mammals.

Inositol-tripyrophosphate is an allosteric effector of hemoglobin due to its ability to cross the plasma membrane of red blood cells and deliver oxygen to solid tumors, by lowering the oxygen affinity of the hemoglobin of red blood cells. The present invention is directed to the use of inositol-tripyrophosphate to reduce hemoglobin's affinity for oxygen in circulating red blood cells. The present invention is further directed to the use of inositol-tripyrophosphate to inhibit angiogenesis and enhance radiation sensitivity of hypoxic tumors. The present invention is further directed to the use of inositol-tripyrophosphate to enhance PO₂ in hypoxic tumors.

The invention belongs to the field of radiotherapy sensibilization medicines, and relates to albumin nanoparticles capable of double-stage oxygen carrying and a preparation method and application thereof. The albumin nanoparticles are mainly prepared from albumin, perfluoro-carbon and catalase, the particle size of the albumin nanoparticles is even, the property is stable, the biosecurity is good,and the problem of radiotherapy resisting of solid tumors can be solved. Experimental results show that the nanoparticles can target the tumors and improve tumor hypoxia by means of double-stage oxygen carrying, for specific performance of double-stage oxygen carrying of the nanoparticles, the high-oxygen-carrying perfluoro-carbon directly supplies oxygen (first stage oxygen carrying) to the hypoxic tumors directly through oxygen concentration gradient difference, meanwhile, the catalase conducts catalytic hydrolysis on high-concentration hydrogen peroxide on the tumor portions to generate oxygen for indirect oxygen carrying (second stage oxygen carrying), through synergism of first stage oxygen carrying and second stage oxygen carrying, a tumor hypoxia microenvironment is reversed, and effective sensibilization is conducted on oxygen-dependent tumor radiotherapy.

The invention relates to a PET tracer agent precursor-2-nitroimidazole compound and a preparation method thereof.The chemical name of the precursor is 2-[4-(carboxymethyl)-7-[2-(2-(2-nitro-1H-imidazole-1-yl)acetylamino)ethyl]-1,4,7-triazacyclononane-1-yl]acetic acid, and the structural formula of the precursor is shown as a formula (I) (please see the formula in the description).The PET tracer agent precursor solves the technical problems that an existing hypoxic imaging agent is complex in labeling operation and low in labeling rate, overcomes the high lipophilicity application defect and is particularly suitable for diagnosis, treatment, treatment effect monitoring and the like of hypoxic tumors.

The invention discloses a branched 2-nitroimidazole compound and application thereof in hypoxic selective antitumor prodrugs. The branched 2-nitroimidazole compound has a structure represented by formula I, wherein R1 and R2 include but are not limited to the following structures: hydrogen and methyl. The branched 2-nitroimidazole compound can be targeted to a hypoxic region of tumor, and is reduced by specific enzymes that are highly expressed in hypoxic tumor tissues to release active drugs. The branched 2-nitroimidazole compound can be connected with ligands and anti-tumor drugs, is appliedto the hypoxic selective antitumor prodrugs, improves the solubility of the drugs, improves the targeting, reduces toxic and side effects, and enhances anti-tumor efficacy.