43 results about "Hypoxic tumor" patented technology

The invention discloses a CAIX targeted degradation agent. The CAIX targeted degradation agent comprises a CAIX target protein ligand, an integrin ligand and a connector, the CAIX target protein ligand and the integrin ligand are connected through the connecting body. As the carbonic anhydrase IX is enriched in the tumor region, the CAIX targeted degradation agent can specifically target the tumor region; the compound can effectively induce degradation of CAIX and inhibit survival of tumor cells under the hypoxia condition, has the functions of targeting a tumor area and degrading carbonic anhydrase IX by utilizing integrin and lysosome, further changes hypoxia and subacid environments of the internal environment of a tumor patient, and plays a role in inhibiting survival of hypoxia tumor cells; the tumor targeting property is high, the toxic and side effects on normal cells are relatively small, and a relatively good effect can be obtained by using a relatively small dosage.

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.

The invention belongs to the field of medicinal chemistry, and particularly discloses a preparation method and application of a nitroimidazole derivative serving as an anti-tumor radiosensitizer. According to the invention, nitroimidazole is used as a lead compound, and a framework of nitroimidazole is modified through a series of reactions to obtain the novel nitroimidazole derivative. The compound can target a tumor hypoxia region, is reduced by a specific enzyme highly expressed in a hypoxia tumor tissue, and is combined with nucleophilic biological macromolecular free radicals generated by radiation to accelerate cancer cell death. As an anti-tumor radiosensitizer, the compound disclosed by the invention is expected to improve the tumor cell selectivity of the compound and reduce toxic and side effects, and is used for subsequent anti-tumor activity research.

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 invention relates to the field of biochemical materials and organic photoelectric information materials, and discloses a near-infrared nitric oxide probe, when the near-infrared probe responds to nitric oxide, a novel phototherapy reagent can be generated, and under the irradiation condition of 550-730 nm near-infrared light, the near-infrared probe can be used for detecting the near-infrared nitric oxide. The phototherapy reagent shows enhanced active oxygen generation capability and performance of continuously releasing nitric oxide, shows remarkably enhanced photoacoustic signals and photo-thermal performance in the nitric oxide releasing process, realizes combined treatment of hypoxic tumors, including hypoxic tumor photo-thermal treatment, I-type photodynamic treatment and nitric oxide mediated gas therapy, and also has the advantages that the phototherapy reagent can be used for treating hypoxic tumors, and the phototherapy reagent can be used for treating hypoxic tumors. After nitric oxide is released, the system can recover to obtain the initial nitric oxide probe, so that the probe has the characteristics of reversible combination and nitric oxide release.

The present invention belongs to the field of biomedical technology, and discloses an organic photosensitive nanomaterial, a preparation method thereof and an application thereof. The organic photosensitive nanomaterial of the present invention has a core-shell structure; the shell structure includes an amphiphilic polymer, and the core structure includes an organic conjugate and an electron sacrificial agent; the preparation method of the organic photosensitive nanomaterial of the present invention includes the following steps: self-assembling the organic conjugate, the electron sacrificial agent and the amphiphilic polymer. Due to its unique structural design and excellent GSH consumption performance, the organic photosensitive nanomaterial of the present invention can consume endogenous GSH in tumor cells, reduce its loss of ROS, and further enhance the oxidative stress in tumor cells; and can jointly regulate the level of GSH in tumor cells and increase the utilization rate of ROS in hypoxic tumors, and is used as a drug regimen for realizing GSH consumption to promote the treatment effect of hypoxic tumors in PDT.

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 present invention discloses a fluorinated zinc phthalocyanine derivative and its preparation method and application. The fluorinated zinc phthalocyanine derivative is obtained by chemically covalently linking trithiocarbonate to the four amino groups of tetraaminoperfluorophthalocyanine zinc. The fluorinated zinc phthalocyanine derivative can be used as a star-shaped RAFT chain transfer agent to induce hydrophobic methacrylate monomers and / or hydrophilic acrylate monomers to prepare four-arm star-shaped random copolymers through near-infrared light-controlled reversible addition-fragmentation chain transfer polymerization. The star-shaped polymer prepared by the above method has a narrow molecular weight distribution and can form polymer micelles with uniform hydrodynamic diameter in an aqueous solution below its critical aggregation concentration. In addition, the above polymer micelles have a high singlet state yield and good oxygen carrying capacity, and can be used for two-photon photodynamic therapy of hypoxic tumors.

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 invention discloses an application of a plasma activation solution in preparation of a drug for enhancing hypoxia tumor radiotherapy sensitivity. Atmospheric pressure plasma generated at low power activates a culture solution DMEM, and acts on tumor cells in a hypoxic state, so that the hypoxic state of the tumor cells can be improved, the activity and clone ability of the hypoxic tumor cells can be inhibited, and the growth of tumors can be inhibited by cooperating with radiotherapy. The plasma activating solution can inhibit the activity of hypoxic colorectal cancer cells and regulate the cell cycle, so that the hypoxic colorectal cancer cell cycle is collected in the G2 / M period, the radiotherapy effect is enhanced, and the plasma activating solution has good safety when being applied in vivo.

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 invention relates to a kind of porphyrin-based metal organic framework sonosensitizer and its preparation method and application, the preparation method includes:With porphyrin ligand, metal source, auxiliary agent and organic solvent as preparation raw material, carried out coordination reaction by hydrothermal method and obtained;The porphyrin ligand is tetra-(carboxylphenyl) porphine, the metal source is ytterbium ion salt or its hydrate, and the auxiliary agent is benzoic acid and polyvinylpyrrolidone. The present invention successfully prepares Yb-TCPP sonosensitizer using solvent thermal method, and I / II type ROS can be produced simultaneously under ultrasound;And Au / Yb-TCPP nanosonosensitizer is obtained by in situ growth Au nanoparticles, it has shorter band gap and abundant oxygen vacancy defects, promotes electron-hole separation and suppresses its recombination under ultrasound, can enhance the generation of I / II type ROS, while Au / Yb-TCPP has catalase-like activity, can react with hydrogen peroxide to realize self-oxygenation, alleviate the impact brought by hypoxic tumor microenvironment, and then enhance SDT efficiency.

The invention relates to a photosensitizer based on a merocyanine structure of a twisted molecular skeleton, the molecular skeleton of the photosensitizer is free of heavy atoms, the photosensitizer has excellent active oxygen generation capability and high killing effect on hypoxic tumor cells, and the photosensitizer belongs to a Type I photosensitizer. The problem that in the prior art, heavy atoms such as I need to be introduced into a molecular skeleton of a merocyanine photosensitizer with high reactive oxygen generation capacity, and consequently dark toxicity is high is solved, and the defect that in the prior art, a Type I photosensitizer with the structure easy to modify lacks is overcome.

The present invention relates to the field of organic synthesis and biomedicine, and discloses a method for directional photocatalytic synthesis and the use of conjugated polymers in the preparation of drugs for treating solid tumors. + Specifically converts it into 1,6-NADH, and uses the properties of the generated 1,6-NADH to regulate the original NAD in hypoxic tumor cells + / NADH balance, disrupting the mitochondrial electron respiratory chain and inhibiting the growth of solid tumors under hypoxic conditions.

The present invention belongs to the field of biomedicine technology, and specifically relates to the preparation of a hypoxia-responsive albumin supramolecular nano-drug delivery system and its application in the treatment of hypoxic tumors. The nano-drug delivery system of the present invention includes an albumin supramolecular nano-carrier with an azocalix[4]arene derivative as the drug-carrying body, a mitochondrial-targeted photosensitizer, and an autophagy inhibitor. The system is prepared by a photo-click chemical reaction between the double bond of the azocalixarene and the albumin after reduction treatment, and has hypoxia-responsive characteristics. At the same time, the nano-drug delivery system can trigger an active oxygen storm effect under the external stimulation of red light in a hypoxic environment, inhibit the growth of hypoxic tumors, and has a fluorescence imaging function. In addition, the preparation process of the new drug delivery system is mild, and it can simultaneously load a combination of multiple drugs, and has the function of integrated diagnosis and treatment, and has broad application prospects in the field of hypoxic tumor treatment.

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.