28 results about "Hypoxic tumor" patented technology

The invention specifically discloses a beta-diketone iridium complex as well as a preparation method and application thereof, and relates to the technical field of biological medicines. The beta-diketone iridium complex provided by the invention has high phototoxicity and low dark toxicity, can be applied to tumor cells as effective PSs of PDT, and is specifically delivered to the tumor cells by taking a traditional Chinese medicine monomer tripterine as a supplement in combination with a nano-targeting delivery technology for photodynamic / immune synergistic treatment of hypoxic tumors.

This invention provides a biomarker for detecting immunotherapy resistance in gastric cancer, its application, a model, and a method for using it. This invention demonstrates the significant impact of the hypoxic tumor microenvironment on immunotherapy resistance in gastric cancer, highlighting the crucial roles of FOXO3a and PD-L1 expression in mediating immune escape mechanisms. By employing an innovative microfluidic tumor chip model, the in vivo hypoxic tumor environment was successfully simulated, revealing how hypoxia-induced upregulation of FOXO3a leads to enhanced PD-L1 expression, thereby resulting in immunotherapy resistance.

The invention provides an acoustic-magnetic dual-mode diagnosis and treatment agent as well as a preparation method and application thereof, and belongs to the technical field of preparation of tumor diagnosis and treatment agents. The acoustic-magnetic dual-mode diagnosis and treatment agent is surface-modified magnetic nanoparticles which contain nano balloon genes and are subjected to Escherichia coli induced expression; the nucleotide sequence of the nano-balloon gene is a sequence shown as NCBI: KC601845.1, escherichia coli in the acoustic-magnetic dual-mode diagnosis and treatment agent as a diagnosis and treatment agent carrier has an active targeting property on a tumor hypoxic region, and bacteria contain a nano-balloon and have an acoustic response characteristic; the escherichia coli surface modified magnetic nanoparticles have a magnetic response characteristic. In acoustic-magnetic dual-mode imaging, firstly, on a real-time ultrasonic contrast monitoring image, a nano air bag expressed in bacteria can generate an enhanced tumor ultrasonic echo signal; secondly, under the action of an external changing magnetic field, the magnetic nanoparticles on the surfaces of the bacteria can generate an enhanced tumor magnetic vibration imaging effect, so that more efficient tumor diagnosis and / or treatment can be realized.

The invention relates to a preparation method of a heavy-atom-free photosensitizer based on a BODIPY dye, the photosensitizer comprises a thiocarbamate light cage, not only can generate singlet oxygen (1O2) under red light irradiation, but also can release carbonyl sulfide (COS), and generates hydrogen sulfide (H2S) under physiological conditions through carbonic anhydrase catalysis. By reasonably adjusting the molecular structure, the singlet oxygen quantum yield and hydrogen sulfide release efficiency of the photosensitizer are remarkably improved. The method is the first case which is reported at present and can simultaneously activate and release the organic optical functional micromolecules of H2S and 1O2 through a single beam of red light. The strategy effectively solves the problem of dependence on oxygen in type II photodynamic therapy (PDT), and further effectively improves the effect of PDT hypoxic tumors. In in-vitro and in-vivo experiments, hydrogen sulfide gas and photodynamic synergic treatment trigger pyroptosis of cells, promote maturation of dendritic cells and stimulate antitumor immune response. Therefore, the invention provides a synergistic treatment strategy combining gas, photodynamic and immunotherapy, and has a remarkable effect in the aspect of hypoxic tumor treatment. The photosensitizer material disclosed by the invention is simple to prepare and low in cost, has a wide application prospect, and particularly provides a solution with huge potential for cancer treatment in the field of biomedicine.

The invention belongs to the technical field of medicine preparation, and particularly relates to a ferroptosis agonist, an anoxia response type nanometer co-delivery system and application thereof. The novel ferroptosis agonist RSL3-ClAc is synthesized by introducing a chloracetyl fragment into an RSL3 molecule, the binding capacity of the novel ferroptosis agonist RSL3-ClAc with GPX4 is remarkably enhanced, and then the ferroptosis induction efficiency is improved. And meanwhile, the RSL3-ClAc and the hypoxia response type photosensitizer TCy5-NO2 are subjected to self-assembly, so that the nano drug delivery system is constructed. According to the nano drug delivery system, the EPR effect and the hypoxia response characteristic of the nano carrier are utilized, the tumor barrier can be effectively broken through, and the focus can be accurately positioned. In a tumor hypoxic microenvironment, the activation of a Try5-NO2 photosensitizer is triggered by nitroreductase (NTR), and RSL3-ClAc is synchronously released to enhance the ferroptosis induction effect.

The application relates to a composite nanogel and a preparation method and application thereof, in particular to the technical field of biomedical materials. The composite nanogel comprises a nanogel framework and tirapazamine and folic acid loaded on the nanogel framework, wherein raw material components of the nanogel framework comprise a temperature-sensitive monomer and a monomer containing a catechol group. The composite nanogel provided by the application can solve the problems that poor blood vessel adhesion of traditional embolic agents easily leads to embolism recanalization, simple physical embolism is difficult to completely remove hypoxic tumor cells, and existing treatment strategies cannot effectively reverse the immune suppression microenvironment after embolism and activate the systemic anti-tumor immune response.

The application discloses a kind of lipid droplet targeted NIR-I photothermal agent and its application in hypoxic tumor treatment, belong to the technical field of photothermal therapy.The NIR-I photothermal agent of the application is a kind of organic photothermal material based on donor-acceptor structure, with strong electron-deficient and rigid planar structure dithiophene pyrrolone sub benzodifuran diketone (BTPDBDF) as acceptor unit, respectively with triphenylamine and tetraphenyl ethylene as donor unit, with strong intramolecular charge transfer, absorption spectrum reaches near infrared region one.Simultaneously, the material is prepared into water-soluble nanoparticles by nano precipitation method, and the biocompatibility and targeting are improved.The nano preparation has the ability of specific targeting cell lipid droplet, and shows significant heating performance and high photothermal conversion efficiency under 808 nm laser irradiation, and shows good near-infrared light capturing capacity, so as to facilitate effective photothermal therapy under the condition of tumor hypoxia.

This invention discloses a class of enzyme-activated prodrug compounds having the following general structural formula I: This invention discloses a class of enzyme-sensitive chlorambucil analog prodrugs. These prodrugs exhibit high selectivity for hypoxic tumors and can be effectively activated within hypoxic tumor cells. Upon specific activation, the prodrug releases free chemotherapeutic drug chlorambucil, simultaneously releasing the photosensitizer cyanine dye, achieving an "OFF-ON" photosensitivity conversion, and generating a large number of reactive oxygen species, thus achieving the unification and synergy of photodynamic therapy and activatable chemotherapy.

The invention discloses a ruthenium complex of targeted carbonic anhydrase as well as a preparation method and application of the ruthenium complex. The complex takes ruthenium (Ru < 2 + >) as a central metal ion, is formed by coordinating a bidentate ligand (An-en) containing an anthracene structure, a pyridine derivative ligand (N-ABS) containing a benzenesulfonamide group and a ruthenium precursor, and has the capability of accurately targeting tumor cell carbonic anhydrase IX (CAIX); the complex is low in dark toxicity and excellent in curative effect in an anoxic environment, the defects that a traditional ruthenium complex is high in dark toxicity and poor in anoxic curative effect can be effectively overcome, and an efficient and low-toxicity new strategy is provided for anoxic tumor treatment.

This invention belongs to the field of pharmaceutical chemistry technology, specifically relating to a near-infrared II luminescent iridium(III) complex photosensitizer, its preparation method, and its application. The near-infrared II luminescent iridium(III) complex photosensitizer disclosed in this invention generates singlet oxygen (…) under 550 nm illumination. 1 O2), hydroxyl radicals (•OH), superoxide anions (O2) •‑ We evaluated the antitumor activity of near-infrared luminescent iridium complexes using mouse breast cancer cells (4T1). Under unilluminated conditions, the near-infrared II luminescent iridium(III) complex photosensitizers showed no significant cytotoxicity to 4T1 cells, while under illumination, they exhibited good phototoxicity to 4T1 cells, with an IC50 value of [missing value]. 50 The concentration is 15.92 μM. We have invented a near-infrared II luminescent iridium(III) complex photosensitizer, which has excellent photoimmunodynamic therapeutic effects and will have important application prospects in the treatment of hypoxic tumors.

The invention discloses a polygonal anthracene functionalized BODIPY supramolecular metal ring compound as well as a preparation method and application thereof, and belongs to the technical field of supramolecular materials, the polygonal anthracene functionalized BODIPY supramolecular metal ring compound is obtained by self-assembly reaction of an anthracene functionalized BODIPY photosensitizer with a specific structure and a platinum compound; by selecting platinum compounds with different coordination included angles, triangular, quadrilateral and hexagonal supramolecular metal ring compounds are respectively prepared. Furthermore, amphiphilic polymer F127 is used for wrapping the supramolecular metal ring compound to form water-soluble nanoparticles, so that phototherapy and chemotherapy combined therapy of hypoxic tumors can be realized, and the amphiphilic polymer F127 has a wide application prospect in the aspects of biological imaging and tumor therapy.

The present application relates to the technical field of nanobiomedicine, and particularly relates to a porphyrin oxygen-carrying polymer sonosensitizer, a preparation method and application thereof; the porphyrin oxygen-carrying polymer sonosensitizer takes porphyrin as a main body structure and takes polyheptafluorobutyramide as a polymer side chain. The polyheptafluorobutyramide contained in the porphyrin oxygen-carrying polymer sonosensitizer can carry oxygen, and under the activation of ultrasound, the perfluoroalkyl-modified polymer can release oxygen explosively, the perfluoroalkyl-modified polymer triggered by visible light increases oxygen supply to relieve tumor hypoxia, reverses a low-oxygen microenvironment, enhances the generation of reactive oxygen species in the SDT process, further improves the accumulation efficiency at a tumor site, improves the effect of SDT in treating tumors, and becomes an effective method for enhancing the chemical sonodynamic therapy of hypoxic tumors.

The present invention relates to a method using low intensity pulsed ultrasound (LIPUS) in order to improve drug delivery efficiency in a hypoxic tumor microenvironment (TME) of cholangiocarcinoma (CCA), and more specifically, to a method for confirming the drug permeability and cancer cell apoptosis of cholangiocarcinoma through the irradiation of low intensity pulsed ultrasound (LIPUS) under a tumor microenvironment, and a combination regimen, of gemcitabine and cisplatin with low-intensity pulsed ultrasound, for inhibiting cholangiocarcinoma growth. To this end, provided is the method for confirming the drug permeability and cancer cell apoptosis of cholangiocarcinoma through the irradiation of low intensity pulsed ultrasound (LIPUS) under a tumor microenvironment, the method comprising: a step (S100) for administering a drug and a fluorescent material to cholangiocarcinoma (CCA) under a tumor microenvironment; a step (S120) for allowing a predetermined time to elapse; a step (S140) for irradiating the cholangiocarcinoma (CCA) low intensity pulsed ultrasound (LIPUS); a step (S160) for acquiring a 3D image by performing tissue-clearing on the cholangiocarcinoma (CCA); and a step (S180) for confirming the in vivo drug permeability of a drug and a fluorescent material from the 3D image.

The invention relates to composite nanogel as well as a preparation method and application thereof, in particular to the technical field of biomedical materials. The composite nanogel comprises a nanogel skeleton, tirapazamine and folic acid, the tirapazamine and the folic acid are loaded on the nanogel skeleton, and raw material components of the nanogel skeleton comprise a temperature-sensitive monomer and a monomer containing a catechol group. The composite nanogel provided by the invention can solve the problems that a traditional embolism agent is poor in blood vessel adhesion and easy to cause embolism recovery, hypoxia tumor cells are difficult to thoroughly remove by pure physical embolism, and an immunosuppressive microenvironment after embolism cannot be effectively reversed and systemic anti-tumor immune response cannot be activated by an existing treatment strategy.

The invention discloses a tumor treatment system based on an ultrasonic fatigue effect, which directly damages a cancer cell membrane structure and destroys the integrity of the cancer cell membrane structure through the continuous action of low-intensity ultrasonic energy, specifically targets a disordered tumor extracellular matrix by utilizing the ultrasonic fatigue effect, and simultaneously causes mechanical damage to tumor blood vessels. The tumor core hypoxia caused by nutrition delivery is blocked, so that cell apoptosis is induced. And the multi-layer mechanical-biological effect jointly inhibits tumor growth. The tumor treatment system is combined with temozolomide for use, can synergistically amplify the anti-tumor effect, and is suitable for hypoxic tumors tolerated by a traditional therapy. According to the treatment system, a non-invasive and controllable tumor treatment mode is achieved through accurate regulation and control of energy, and a new thought is provided for tumor treatment.

This invention relates to the field of cell culture technology, and discloses a method for culturing NK cells and its applications. When NK cells enter a hypoxic environment, not only do their cytotoxic activity and proliferative capacity rapidly decline, but they also experience metabolic disorders such as impaired mitochondrial function, insufficient ATP production, and abnormal accumulation of reactive oxygen species (ROS), leading to functional failure and limiting their application in tumor therapy. Existing technologies mainly rely on constant or single-stage hypoxia induction, failing to improve the insufficient hypoxia adaptation of NK cells at the metabolic level. Therefore, this invention provides a method that uses repeated acclimatization culture with gradually decreasing oxygen concentration to allow NK cells to gradually adapt to the metabolic demands of a hypoxic environment. NK cells cultured using this method exhibit a more stable metabolic state and superior cytotoxic activity in a hypoxic environment, significantly enhancing their anti-tumor efficacy and solving the problem of metabolic imbalance and rapid functional loss of NK cells in the hypoxic tumor microenvironment in existing technologies.

The invention discloses a pharmaceutical composition for tumor embolism treatment. The pharmaceutical composition consists of a tirapazamine derivative RTPZ and iodophol. The preparation method comprises the following steps: S1, dissolving tirapazamine and an alkaline substance in a solvent, and adding alkyl acyl chloride for reaction until the raw materials are completely converted; s2, after the reaction in the S1 is finished, performing rotary evaporation to remove the solvent, adding dichloromethane for dissolving, washing with a saturated saline solution, drying with anhydrous sodium sulfate, and finally evaporating to remove the solvent to obtain a crude product; s3, purifying the crude product to obtain RTPZ; and S4, directly dissolving the RTPZ in the iodinated oil until the RTPZ is saturated. According to the invention, the characteristics of a high oil-soluble drug, an iodized oil embolism agent and slow release are integrated, a local, slow-release and target hypoxic tumor treatment system for transcatheter arterial chemoembolization is constructed, an anti-tumor effect far better than that of a raw drug TPZ is achieved on a VX2 rabbit tumor embolism model, and a microenvironment after embolism can be effectively regulated and controlled.

The application relates to the field of biological medicine, and relates to a method for enhancing the tumor killing effect of NK cells and application, in particular to a method and application of fraxidin in enhancing the tumor killing effect of NK cells; through experiment verification, it is proved that the fraxidin can improve the killing ability of NK cells to tumor cells under the hypoxic tumor microenvironment, and up-regulate the expression of active molecules on the surface of NK cells and NK cell activation receptors; the fraxidin is used to regulate the NK activity for the first time, and the method has important significance.

This invention discloses a tumor cell hypoxia-sensitive fluorescent probe, its preparation method, and its application, belonging to the field of biomedical application technology. The tumor cell hypoxia-sensitive fluorescent probe provided by this invention uses triazine as the response unit, responding to the cellular microenvironment and being sensitive to hypoxia. It exhibits a significant specific activation effect in hypoxic tumor cells, enabling precise and efficient identification of hypoxic tumor cells.

The present disclosure relates generally to the field of medical devices. In particular, the present disclosure relates to devices, systems and methods for improved efficacy of radiotherapy treatment of hypoxic tumors. For example, the disclosed devices, systems and methods may statically or continuously oxygenate hypoxic tumors immediately prior to or simultaneous with irradiation.

This invention discloses a binary phthalocyanine exhibiting type I photosensitivity and photothermal synergistic effects, its preparation, and its applications. The binary phthalocyanine is a silicon phthalocyanine-zinc phthalocyanine coupling compound or a zinc phthalocyanine-zinc phthalocyanine coupling compound, which can self-assemble in water. In water, the self-assembled binary phthalocyanine not only produces an effective type I photosensitivity reaction but also generates a photothermal effect, thus it can be used as a photosensitizer, photothermal agent, or photodynamic-photothermal combined drug. Furthermore, when used as a photodynamic-photothermal combined drug, it can generate a high amount of superoxide anions and a significant photothermal effect under near-infrared laser irradiation and hypoxic conditions, meaning it has high anticancer activity under both aerobic and anaerobic conditions, showing significant application prospects in the treatment of hypoxic tumors. In addition, in vivo experiments have demonstrated that the binary phthalocyanine can be cleared by the kidneys and excreted in urine, effectively avoiding potential biotoxicity caused by drug accumulation after treatment, thereby significantly improving biosafety.

This invention relates to a method for preparing and applying a nanoprobe for multimodal imaging and synergistic therapy, belonging to the field of bioprobe technology. The method includes: loading the acoustic sensitizer MnTTP and the hypoxia-activating drug TPZ onto PLGA via an emulsion-solvent evaporation method, modifying it to an aqueous phase using PVA, using dopamine hydrochloride to increase biocompatibility, obtaining the nanoprobe TMP@D, and then... (The sentence is incomplete in the original text). 131 I-labeling on TMP@D yields radionuclide-loaded nanoprobes. 131 I-TMP@D. 131 I-TMP@D passively targets and enters tumor cells, enabling synergistic treatment of malignant hypoxic tumors by combining MR and SPECT multimodal imaging with radionuclide therapy, sonodynamic therapy, and hypoxia-activated chemotherapy.

The application discloses a kind of photodynamic driven chemotherapy nano-drugs for hypoxic tumor treatment and its preparation method and application in treating solid tumor.The nano-drug described in the application has the following significant features: uniform particle size distribution, good stability;High efficiency produces superoxide anion and releases drug, continuously consumes local oxygen under light condition, thereby further intensifies the hypoxic state of tumor, enhances the effect of hypoxic activated drug, realizes the positive feedback synergistic effect of photodynamic driven chemotherapy, simultaneously induces cell to occur immunogenic cell death;By folate modification, the active targeting of nano-drug to tumor site is realized, and tumor growth is inhibited.

The application discloses a nano prodrug for releasing nitric oxide gas by ultrasonic piezoelectric catalysis effect and a preparation method and application thereof. 2000 The nano prodrug is formed by covalently coupling a nitric oxide precursor poly-L-arginine and a phospholipid DSPE-PEG -NH2 through an amidation reaction to form an amphiphilic prodrug molecule, and then encapsulating a nano piezoelectric material barium titanate to form the nano prodrug, which is accumulated in tumor tissues through enhanced permeation and retention effect, and generates a piezoelectric effect by using ultrasonic waves to stimulate the barium titanate, so that water molecules generate singlet oxygen, hydrogen peroxide and oxygen, and then the polyarginine is oxidized to release nitric oxide; the process is independent of oxygen and can produce oxygen, and is suitable for treatment of hypoxic tumors. The application further discloses application of the nano particles in breast cancer treatment, and the nano particles have good biocompatibility and remarkable effects of inhibiting tumor growth and metastasis, and have an advantage of being not limited by a tumor microenvironment compared with existing NO controlled release technology.

The invention relates to the technical field of medical medicines, in particular to a compound oral preparation containing m-BPA and metronidazole as well as a preparation method and application of the compound oral preparation. The compound oral preparation comprises a medicine core and a coating completely coating the medicine core, wherein the medicine core is prepared from the following raw materials in parts by weight: 600 parts of m-BPA, 150 to 300 parts of metronidazole, 135 to 150 parts of microcrystalline cellulose, 25 to 35 parts of hydroxypropyl methylcellulose, 15 to 20 parts of polyvinylpolypyrrolidone, 2.5 to 3.5 parts of vitamin C and 15 to 17 parts of magnesium stearate. The compound oral enteric-coated granule taking m-boron phenylalanine as a boron source and metronidazole as a hypoxic sensitizer is suitable for BNCT synergistic treatment of LAT1 high-expression hypoxic solid tumors (head and neck tumors, melanoma and pancreatic cancer), and can realize a simplified treatment process of'single oral administration + neutron irradiation '; the boron drug and the sensitizer are ensured to synchronously reach the peak, and the hypoxic tumor cells are synergistically killed.

The invention relates to the technical field of biomedical materials and drug delivery systems, in particular to a polyethylene glycol density-adjustable membrane fusion liposome as well as a preparation method and application thereof. The membrane fusion liposome with the adjustable polyethylene glycol density is HC-Lips (at) siATG5. In the liver, due to high PEG coverage, the uptake efficiency of the membrane fusion lipidosome in liver Kupffer cells is low, and the membrane fusion lipidosome enters cells through an endosome / lysosome way, so that most of siATG5 is degraded; the part of PEG connected through azobenzene on the surfaces of hypoxic tumor tissues and the membrane fusion liposome falls off and exposes the surface, and then under the guidance of CRV peptide ligands, the part of PEG and tumor-related macrophages enriched in a tumor hypoxic region are subjected to membrane fusion, and siATG5 is directly released to cytoplasm by bypassing a lysosome way. Through hypoxia regulation and control of the surface PEG density, the membrane fusion liposome can selectively deliver siATG5 to TAMs. By efficiently delivering siATG5 to TAMs, the liposome can repolarize M2 type macrophages into M1 type macrophages, remodel a pancreatic cancer immunosuppression microenvironment and activate anti-cancer immune response.

This invention discloses a nano-heterojunction radiosensitizer suitable for hypoxic tumors and its preparation method. The radiosensitizer is a core-shell structured nanoparticle, comprising a core and a shell. The core is a high-valence bismuth-based nanomaterial, including at least one of sodium bismuthate, silver bismuthate, and potassium bismuthate. The shell coats the surface of the core and comprises a metal oxide. A Z-shaped heterojunction is formed between the inner core and the outer shell. Under X-ray excitation, this heterojunction forms a built-in electric field, promoting electron-hole separation. Electrons in the high-valence bismuth nanoparticle phase reduce high-valence bismuth (Bi). 5+ →Bi 3+ ) and releases highly reactive lattice oxygen, which then reacts with holes on the TiO2 phase to generate singlet oxygen ( 1 O2), while the holes on TiO2 oxidize water molecules to produce hydroxyl radicals (•OH).

The present invention provides fluorescent carbon nanodots with a Type I PDT effect, as well as their preparation method and application, belonging to the field of materials chemistry. Using biologically derived hemin as a raw material, the present invention produces fluorescent carbon nanodots with a Type I PDT effect through a simple and convenient solvothermal reaction, dialysis to remove impurities, and drying. These nanodots exhibit uniform size, stable fluorescence emission, good biocompatibility, low toxicity, and excellent Type I PDT effect. They are widely applicable to Type I PDT or combined therapy for hypoxic tumors guided by precise imaging.