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 relates to the use of adenosine receptor antagonists, preferably A3 receptor antagonists, either alone or in combination with other agents for the treatment, prevention and / or management of diseases or disorders associated with overexpression of HIF-1α and / or increased HIF-1α activity (e.g., cancer, respiratory disease). The methods and compositions of the invention are particularly useful for preventing, treating, or ameliorating symptoms associated with a cancer, disease or disorder associated with hypoxia-inducible factor 1α (HIF-1α) using the A3 receptor antagonists of the invention. The present invention provides methods to inhibit the growth of tumors, particularly solid tumors and more particularly hypoxic tumors.

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.

Methods and systems for treatment of hypoxic tumors are provided, including the steps of positioning a delivery device in a bodily cavity adjacent to tumor tissue, delivering an oxygenating agent to the tumor tissue via the delivery device and radiating the tumor tissue with radiation. Methods and systems of treatment of tumors are also provided, including the steps of positioning a delivery device in a bodily cavity adjacent to tumor tissue, delivering a photosensitizing agent to the tumor tissue via the delivery device, and radiating the tumor tissue with light.

The invention provides a nitroreductase-specific fluorescent probe and the preparation thereof and a reagent for applying the nitroreductase-specific fluorescent probe to tumor-targeted fluorescence imaging and monitoring of tumor hypoxia. The reagent is connected by tumor biomarker identifying groups (sensor), tumor targeted groups (target) and fluorescent groups (dye) via chemical bonds. The reagent can be used in the tumors with hypoxic microenvironment and high expression of nitroreductase based on tumor hypoxia and the high expression of nitroreductase in hypoxic tumors. Combined with a fluorescence imager, the reagent can be used in tumor targeted fluorescence imaging, tumor hypoxia monitoring and the monitoring of tumor metastasis, etc. The reagent realizes high sensitivity and high specificity in application and provides an effective tool for medical study of cancer and clinical monitoring and treatment of tumor metastasis, thereby having a good application prospect in tumor-targeted fluorescence imaging, tumor hypoxia monitoring and monitoring of tumor metastasis.

The invention relates to the field of new materials for cancer treatment, in particular to singlet oxygen (1O 2) controlled-release carbon quantum dots (CDs) and a preparation method and application thereof. The CDs have a strong ability of capturing 1O 2, and can release the captured CO2 under heating or ultrasound conditions for efficient treatment of hypoxic tumors. At the same time, the CDs have the advantages that the photothermal conversion efficiency is high, the photostability and biocompatibility are excellent, the synthesis process is simple, raw materials are easy to obtain, and thecost is low, and the single oxygen controlled-release carbon quantum dots can be used as new materials for cancer treatment.

The invention discloses a polyboron phenylalanine compound containing nitroimidazole as shown in a general formula (I) in the specification or pharmaceutically acceptable salt thereof, as well as a preparation method and application thereof. The compound can be prepared through substitution, addition, nitrification and deprotection reactions, and has the advantages of low cost, easy preparation, high content boron, high affinity for tumor cells, specific response for hypoxic tumor area, good stability and low biotoxicity. The medicinal composition containing a boron compound has a relatively good application prospect in BNCT.

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 present invention relates to novel radioactively labeled bioreducible tracers of Formula I useful for detecting hypoxic tumors or ischemic tissue in vivo. In one embodiment, the tracers consist of a 2-nitroimidazole moiety, a triazole, metabolically stable linker with pharmacokinetics enhancing substituents, and a radioisotope. The preferred in vivo imaging modality is positron emission tomography.

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 invention discloses a hypoxia-activated prodrug based on 2-nitroimidazole-1-alkanol. The 2-nitroimidazole-1-alkanol of the prodrug is connected to an antineoplastic drug through a carbonate bond. The prodrug has a structure shown in the formula I and in the formula, n represents 0, 1, 2 or 3, and R1, R2, R3 and R4 include but not limited to hydrogen, hydroxyl, chlorine, bromine, fluorine, C1-C6 alkyl, C1-C6 alkyl containing alkenyl and C1-C6 alkyl containing alkynyl. The prodrug can target the hypoxia region of the tumor and is reduced by the high expressed specific enzyme in the hypoxic tumor tissue so that the original drug is released. The prodrug is stable in vitro and in vivo, and the released drug can be specifically reduced in hypoxic tumor tissue so that the targeting of the anti-tumor drug is improved, toxic or side effects are reduced and the curative effect is improved.

Methods and systems for treatment of hypoxic tumors are provided, including the steps of positioning a delivery device in a bodily cavity adjacent to tumor tissue, delivering an oxygenating agent to the tumor tissue via the delivery device and radiating the tumor tissue with radiation. Methods and systems of treatment of tumors are also provided, including the steps of positioning a delivery device in a bodily cavity adjacent to tumor tissue, delivering a photosensitizing agent to the tumor tissue via the delivery device, and radiating the tumor tissue with 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.

Novel phosphate-bearing prodrugs of sulfonyl hydrazines have the formula presented below. 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 is C1-C10 alkyl or haloalkyl;R′ and R″ are each independently C1-C10 alkyl;R1 is CH3; andX is O;or a pharmaceutically acceptable salt, solvate, polymorph or metabolite thereof.

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=C1-10 alkyl, or C1-10 haloalkyl (preferably containing no more than 5 halogen groups, preferably 2-chloroethyl); R′ and R″ are independently C1-10 alkyl, or C5-20 aryl or heteroaryl (preferably methyl); R1 is H, C1-10 alkyl, C1-10 alkoxyl, C5-20 aryl or heteroaryl or C5-20 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 formulaR-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 provides a preparation method and application of a hypoxic tumor region targeted short chain polypeptide micromolecule self-assembly nanometer material. The nanometer material is a shortchain polypeptide modified micromolecule carbonic anhydrase inhibitor, wherein an N end of short chain polypeptide is combined with a substituted or unsubstituted aromatic group. Through targeting carbonic anhydrase expressing film height of hypoxic tumor cells, tumor microenvironment in situ responsive self-assembly is realized, and specific internalization of the hypoxic tumor cells is induced,so that the hypoxic tumor cells are adjusted, controlled, killed and damaged. The material is simple in preparation technology, has higher biological safety biological safety, can effectively kill and damage the hypoxic tumor cells, can significantly improve conventional clinical chemotherapy treatment effects, can retard tumor metastasis process and can provide more thinking and means for clinical tumor treatment.

The invention discloses a delivery system based on nano-liposome, a preparation method and an application thereof. The nano-liposome is of a granular structure composed of a shell layer and emulsion in the shell layer. The shell layer is composed of lecithin and cholesterol, and the emulsion is composed of perfluorocarbon and Tween-80; wherein the mass ratio of lecithin to cholesterol is (1-4): (0.5-1); the volume ratio of the perfluorinated carbon to the tween-80 is (1-6): (0.5-1.5); and the average particle size of the liposome is 100 nm to 300 nm. The preparation method comprises the following steps: firstly, perfluorocarbon is prepared into an emulsion, and then the emulsion is wrapped in a liposome; when the liposome is combined with ozone, the ozone is coated in the liposome, so that the stability of the ozone and the concentration of the carried ozone are improved; the nano-liposome loaded ozone is specifically delivered into a tumor microenvironment, under the action of rays, the ozone can be decomposed into hydroxyl radicals with higher concentration compared with oxygen, the effect of directly killing tumor cells is achieved, meanwhile, the ozone can also be decomposed to generate oxygen, and the killing sensitivity of radioactive rays to the tumor cells is enhanced by improving the hypoxic tumor microenvironment.

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 = C1-10 alkyl, or C1-10 haloalkyl (preferably containing no more than 5 halogen groups, preferably 2-chloroethyl); R' and R'' are independently C1-10 alkyl, or C5-20 aryl or heteroaryl (preferably methyl); R1 is H, C1-10 alkyl, C1-10 alkoxyl, C5-20 aryl or heteroaryl or C5-20 aroxyl or heteroaroxyl (preferably methyl and ethyl); X is O, NH, or NR (preferably O); Y is (CH2)n , where n = 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.

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.

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.