89 results about "Tumor hypoxia" patented technology

The invention discloses a polyethylene glycol modified gold and manganese dioxide nano particle and a preparation method and application thereof, and belongs to the technical field of biological medicine, the polyethylene glycol modified gold and manganese dioxide nano particle (GMCN and PEG) has good biocompatibility under neutral physiological conditions, can relieve tumor hypoxia and increase generation of active oxygen in acidic TME, and has a good anti-tumor effect. The radiotherapy sensitivity is improved; and immune cell death is induced. Meanwhile, a cGAS-STING signal channel can be activated, dendritic cell maturation, macrophage M1 polarization and T cell infiltration are promoted, and the immunosuppression state in TME is counteracted. In addition, the GMCN-coated PEG also has an MR-CT bimodal imaging enhancement function, and integration of diagnosis and treatment is realized. The nano sensitizer disclosed by the invention has huge potential in the aspects of improving the radiotherapy curative effect, remodeling the tumor microenvironment, promoting the anti-tumor immunity, enhancing the biomedical imaging and the like.

The invention relates to a tirapazamine-loaded phosphorus-containing dendrimer / protein compound for inducing tumor mineralization as well as a preparation method and application thereof, the compound takes diphosphonate-terminated phosphorus-containing dendrimer AK176 as a carrier, and the carrier is loaded with protein and medicine. The nano-drug can target tumor cells through FN and form a biomineralization layer in the peripheral area of tumor tissues, and a tumor hypoxic microenvironment is intensified, so that the pharmaceutical activity of tirapazamine is activated, and cooperative treatment of blocking treatment / chemotherapy of triple-negative breast cancer is realized.

The invention relates to a MnO2 in-situ coated nano diamond drug, which is prepared by the following steps: by taking nano diamond as a carrier, modifying the surface of the nano diamond with polylysine so as to improve the dispersity and provide amino groups, then connecting the nano diamond with glucose oxidase rich in carboxyl groups through an amide reaction, and then coating the surface of the nano diamond with MnO2 through KMnO4 reduction so as to obtain the MnO2 in-situ coated nano diamond drug. Finally, the chemotherapeutic drug DOX is loaded through coordination and electrostatic interaction. According to the nano diamond medicine, in a subacid tumor microenvironment rich in GSH, the wrapped MnO2 shell is subjected to a redox reaction to generate Mn < 2 + >, meanwhile, the MnO2 nano structure can trigger H2O2 in the tumor microenvironment to be decomposed to generate O2, tumor hypoxia can be relieved, GOx can be exposed, glucose in a tumor area can be effectively catalyzed to generate H2O2 under the aerobic condition, and therefore the tumor hypoxia can be relieved. Glucose consumption effectively cuts off nutrition sources of tumor cells, inhibits tumor cell proliferation and realizes tumor hunger treatment. According to the invention, chemotherapy, hunger therapy and chemical kinetics therapy are cooperated to efficiently and selectively kill tumor cells, and a remarkable anti-tumor effect is achieved.

The invention relates to a tumor hypoxia specific response BODIPY fluorescent probe as well as preparation and application thereof. The invention relates to a BODIPY fluorescent probe which is synthesized by utilizing tumor hypoxia to respond to azobenzene groups. The probe has no signal to normal oxygen cells, shows strong near-infrared fluorescence to hypoxia cancer cells, and can be used for visually detecting deep solid tumors. According to the present invention, the tumor specific response BODIPY fluorescent probe is adopted as the research object, the human liver cancer cells (HepG2) and the human non-small cell lung cancer cells (A549) are adopted as the tested cell strains, the fluorescence detection ability research under the normal oxygen and oxygen deficiency conditions is developed, and the foundation is established for the real-time accurate tumor detection. The fluorescent probe has the advantages of lower preparation cost, simpler synthesis method, easily available raw materials, less side reaction, high yield, easiness in purification, easiness in industrial production and the like.

The application belongs to the technical field of biomedical engineering, and specifically discloses a nano gene composition for treating brain glioma and a preparation method thereof, which is synthesized from bovine serum albumin loaded manganese dioxide particles, PLGA, DSPE-PEG3000 and DSPE-PEG-Angiopep2 as raw materials; the average particle size of the nano gene composition is 122.18±31.3 nm. The application also discloses a preparation method of the nano gene composition. The nano gene composition provided by the application encapsulates miRNA-138 in PLGA to avoid the degradation of miRNA-138 by RNA enzymes in the body, and simultaneously utilizes the targeting property of Angiopep2 to target the delivery of the nano gene composition to tumor tissues, to deliver microRNA into the brain while reducing tumor hypoxia and increasing the sensitivity of cells to X-ray irradiation, so as to realize multidirectional comprehensive treatment of glioblastoma.

The invention relates to a hybrid nano assembly for dual synergistic chemotherapy as well as a preparation method and application of the hybrid nano assembly, and belongs to the technical field of pharmaceutical preparations. The invention relates to a hybrid nano assembly for dual synergistic chemotherapy, which is formed by co-assembling a cabazitaxel prodrug and gossypol under hydrophobic action and hydrogen bond driving, and is modified by adopting a PEG (Polyethylene Glycol) modifier, the molar ratio of the cabazitaxel prodrug to the gossypol is 1: (1-7), and the ratio of the total mass of the cabazitaxel prodrug and the gossypol to the mass of the PEG modifier is 4: 1. A cabazitaxel prodrug and a sensitizer gossypol are co-assembled to obtain a hybrid nano assembly, the hybrid nano assembly is oxygenated to obtain the oxygen-carrying preparation, the nano assembly and the oxygen-carrying preparation are simple and convenient to prepare and high in drug loading efficiency, and efficient co-loading of drugs can be achieved; meanwhile, the curative effect of chemotherapy can be enhanced through dual mechanisms of relieving tumor hypoxia and promoting tumor apoptosis, and the pharmaceutical composition has a good clinical application prospect.

The invention provides a diagnosis and treatment integrated nano platform as well as a preparation method and application thereof. According to the diagnosis and treatment integrated nano platform, an organic-inorganic nano hybrid is constructed through structure optimization and function integration, four modes of PTT, PDT, SDT and CDT are organically combined innovatively, and efficient synergistic treatment of GBM is achieved through real-time monitoring of photoacoustic imaging. First, a dOMV encapsulation strategy significantly improves the ability to penetrate through the blood brain barrier. Meanwhile, the IEICO-4F has a strong near-infrared absorption characteristic and has a synergistic effect with the high catalytic activity of the mesoporous platinum nanoparticles. Under the laser / ultrasonic excitation condition, the diagnosis and treatment integrated nano platform shows excellent photo-thermal conversion performance, the Fenton reaction rate can be increased, endogenous hydrogen peroxide can be continuously catalyzed to be decomposed to generate oxygen, and the tumor hypoxia state is effectively relieved. The series of reactions further enhance the generation of ROS, activate a Caspase-1 / GSDMD mediated pyroptosis pathway, finally achieve an efficient tumor inhibition effect, and successfully break through the limitation of a single treatment mode.

The application discloses a kind of Man-PFH-ICG@PLGA nanoparticles and preparation method and application thereof, belong to composite material preparation technical field.The application uses PLGA as carrier, using polylactic acid-glycolic acid (PLGA) nanoparticles (NPs) to mark the surface of it with mannose, and ICG and oxygen-carrying PFH are embedded therein, the obtained Man-PFH-ICG@PLGA nanoparticles have excellent targeting effect on the overexpression of mannose receptor on the surface of tumor cells, significantly promote the effective endocytosis of cells in vitro and tumor enrichment in vivo, directly relieve the hypoxic environment of tumor;It can also supplement oxygen by endogenous, to activate the TRPA1 channel overexpressed on the surface of tumor cells by ROS generated by cells, so as to inhibit cell respiration, reduce oxygen consumption, indirectly relieve the hypoxic environment of tumor, effectively inhibit the growth of tumor cells, and provide a new idea for clinical exploration of antitumor therapy.

The present disclosure generally relates to novel multiple target inhibitor of tyrosine kinases (TKs) which can suppress angiogenesis, metastasis, oncogenesis, and / or immune regulation activities by inhibiting TKs and have very potent immunomodulatory activity. The present disclosure also relates to a method of using the tyrosine kinase inhibitors, alone or in combination with HDAC inhibitor, for the treatment of cancers, in particular in cancer immunotherapy, by regulating the tumor microenvironment, including reducing tumor hypoxia, reducing lactic acid accumulation, activating CTL, inhibiting the number and activity of immunosuppressive cells, finally obtaining superior anti-cancer benefits and / or producing lasting immune memory.

The present disclosure generally relates to compounds of formula (I) which are multiple target inhibitors of tyrosine kinases (TKs) and which can suppress angiogenesis, metastasis, oncogenesis, and / or immune regulation activities by inhibiting TKs and have very potent immunomodulatory activity. The present disclosure also relates to a method of using said tyrosine kinase inhibitors, alone or in combination with HDAC inhibitor, for the treatment of cancers, in particular in cancer immunotherapy, by regulating the tumor microenvironment, including reducing tumor hypoxia, reducing lactic acid accumulation, activating CTL, inhibiting the number and activity of immunosuppressive cells, finally obtaining superior anti-cancer benefits and / or producing lasting immune memory.

The invention relates to the technical field of tumor treatment, in particular to a phenolic thiazinyl photosensitizer conjugated with different planar electrons as well as a preparation method and application thereof, and the general formula of the phenolic thiazinyl photosensitizer is as follows: # imgabs0 #. The photosensitizer can solve the problems of poor light penetrability of the photosensitizer and poor fluorescence imaging capability, low curative effect and the like caused by a tumor hypoxic microenvironment in the prior art.

The present application relates to the technical field of drug delivery system, and particularly relates to a double-targeting micro-nano robot based on probiotics and framework nucleic acid and a preparation method thereof.In the present application, a drug is introduced into an ECN engineering bacterium (ECN-pl) with a tumor hypoxic microenvironment lysis function as a delivery strategy, which can avoid the activity resistance brought by surface modification of the strain; after entering the body, the DOX@FDN-A2.2@ECN-pl penetrates into the tumor core and senses the lysis protein generated by the tumor cell anoxia, destroys the ECN structure, and thus successfully releases the DOX@FDN-A2.2 to the tumor core; wherein the AS1411 and S2.2 aptamer on the surface of the FDN-A2.2 have the ability to target tumor cells, so the double-targeting aptamer on the surface of the FDN-A2.2 improves the uptake rate of the tumor cells; the problem of tumor drug resistance is overcome, thereby inhibiting the growth of tumor cells.

The present invention discloses a tumor-activated sorafenib prodrug, its preparation method, and its application, belonging to the field of biomedicine technology. The present invention designs a tumor-activated sorafenib prodrug, composed of sorafenib and ferrocenecarboxylic acid molecules as its main structure. It can specifically activate cytotoxicity at the tumor site, and compared to sorafenib, it is more effective in killing liver cancer cells. Furthermore, it undergoes an in situ Fenton reaction, generating oxygen to alleviate tumor hypoxia and reduce tumor invasion and migration. The Fenton reaction can generate highly toxic hydroxyl radicals, which kill liver cancer cells and provide auxiliary treatment.

The utility model relates to a radio-frequency excitation control device for tumor hypoxia research, which comprises a mounting frame, a radio-frequency signal excitation module is mounted on the upper side of the left part of the mounting frame, a radio-frequency signal control module is mounted on the upper side of the right part of the mounting frame, and the radio-frequency signal control module is electrically connected with the radio-frequency signal excitation module. An electric push rod is mounted on the right side of the mounting frame, a lifting table is connected to the telescopic end of the electric push rod, a radio frequency coil is connected to the lifting table, and the radio frequency coil is also electrically connected with the radio frequency signal control module. The electric push rod drives the lifting platform to vertically move, the radio frequency coil is driven to accurately adjust to a target height, and a radio frequency field uniformly covers a sample area, so that test requirements of samples of different specifications are met, an electromagnetic environment is closed by the protective frame, test safety is favorably improved, influence of electromagnetic diffusion on the test is prevented, and test efficiency is improved. Meanwhile, an operator can observe the test condition in real time through the transparent structure in the middle of the protective frame.

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 invention belongs to the field of new auxiliary materials and new dosage forms of pharmaceutical preparations, and relates to a preparation method and application of a co-assembled nano preparation for targeting glioblastoma. The preparation method comprises the following steps: firstly, synthesizing a nitroimidazole dimer with tumor hypoxia-oxidation-reduction triple response, and assembling the nitroimidazole dimer with AOH1996 and HRO761 to prepare the nano preparation. The molar ratio of the AOH1996 to the HRO761 to the nitroimidazole dimer is 1 to 2 to (0.5 to 2). The key scaffold protein PCNA for DNA repair is blocked by the PCNA inhibitor AOH1996, and recruitment and anchoring functions of the key scaffold protein PCNA on repair factors are destroyed, so that the glioblastoma is induced to enter a mismatch repair defect state. On the basis, a WRN inhibitor HRO761 is further used for promoting large-scale breakage of chromosomes and finally inducing cell death. The nitroimidazole dimer and the nitroimidazole dimer are jointly assembled into the nano preparation, and accurate drug release is realized in response to a hypoxia state and oxidation and reduction signals overexpressed in a tumor microenvironment, so that the heterogeneity of the tumor microenvironment is overcome.

The application discloses a preparation method of a multi-charge electrostatic self-assembled nanocomposite and application thereof, and relates to the technical field of nanomaterials. The method comprises the following steps: (1) synthesizing CAT-Ce6; (2) synthesizing negative electric Ag2S-3MPA QDs; (3) synthesizing positive electric Ag2S-NH2 QDs; and (4) preparing Ag2S@CAT-Ce6@Oxa nanocomposite: ultrasonic mixing of Ag2S-NH2 QDs solution and CAT-Ce6 solution to obtain a mixed solution, dropwise adding Oxa dissolved in a mixture of methanol and DMSO into the mixed solution, stirring in a dark environment at room temperature to obtain Ag2S@CAT-Ce6@Oxa crude product, and purifying the Ag2S@CAT-Ce6@Oxa crude product to obtain Ag2S@CAT-Ce6@Oxa nanoparticle pure product. The application is helpful to realize controllable release of drugs, improve curative effect, effectively relieve tumor hypoxia in vivo, provide a better environment for photodynamic therapy and other treatments, realize accurate positioning and observation of tumors, effectively inhibit tumor growth and prolong survival time, improve curative effect and reduce side effects, and has good biocompatibility and wide application prospect in vivo.

The present invention discloses a spatiotemporally controllable drug delivery system targeting the tumor extracellular matrix and its application. The delivery system includes: i) nanoparticles loaded with drugs using a metal polyphenol network modified with polyvinylpyrrolidone as a carrier; and ii) a metal ion chelator; the nanoparticles are used for targeted tumor delivery of drugs; the metal ion chelator is used to disassemble the nanoparticles when they reach the tumor extracellular matrix to release the drugs, thereby degrading the tumor extracellular matrix, enhancing blood perfusion, relieving tumor hypoxia, promoting drug penetration and T cell infiltration to reshape the tumor microenvironment. The present invention provides a novel delivery strategy for drugs targeting the tumor extracellular matrix, effectively overcoming the problem of insufficient treatment such as PDT caused by the TME. It provides new ideas for drug delivery targeting the tumor extracellular matrix and the treatment of various solid tumors.

The invention belongs to the field of biological medicine, and particularly relates to a high-selectivity sensitizer for solid tumor radiotherapy and a preparation method thereof.The sensitizer comprises two newly-designed modified compounds: a derivative based on a diamino-anthraquinone structure and capable of enhancing radiation energy deposition and relieving tumor hypoxia; and the other one is a cystamine derivative containing a diselenide bond, and can effectively consume overexpressed glutathione in tumor cells and enhance the generation of active oxygen. The preparation method comprises the following steps: dissolving the two modified compounds and the biodegradable polymer in an organic solvent to form an organic phase, dissolving phospholipid polyethylene glycol amino in warm water, blending with a stabilizer in a buffer solution to form a water phase, dropwise adding the organic phase into the water phase through a nano-precipitation method, self-assembling to form nano-particles, and filtering and purifying to obtain a final product. The sensitizer can specifically target tumor tissues, the radiotherapy effect is remarkably improved through a multiple synergistic mechanism, meanwhile, the damage to normal tissues is reduced, the preparation process is simple and convenient, and the reproducibility is good.

The invention discloses a pH and enzyme dual-response type targeted DNA nano-carrier for relieving tumor cell hypoxia as well as a preparation method and application of the pH and enzyme dual-response type targeted DNA nano-carrier. The DNA nano-carrier comprises m tandem repeat units, each tandem repeat unit comprises a long single-stranded DNA repeat unit, three complementary short single-stranded DNAs and siRNA, each of the three complementary short single-stranded DNA sequences comprises a functional region and a base complementary region, and the functional region is a pH-responsive nucleic acid complementary sequence or a nucleic acid aptamer sequence for specifically targeting cancer cells; siRNA is a gene therapeutic agent for relieving tumor hypoxia, an extended positive-sense strand of siRNA comprises a 5 '-terminal extended pH response sequence and a positive-sense strand, and the 5'-terminal extended pH response sequence is complementary with a pH-responsive nucleic acid complementary sequence of the complementary short single-stranded DNA. The nano-drug carrier has excellent drug loading capacity and targeting property, can deliver anti-cancer drugs such as siRNA in a targeted manner, responds to a slightly acidic / enzyme environment of tumor cells and is quickly released, and the anti-tumor treatment effect is improved.

The invention relates to a thermo-sensitive hydrogel drug sustained-release stent for jointly loading a hypotensive drug and a chemical / immunotherapy drug, which is prepared from a thermo-sensitive material and loads three drug components, namely losartan, oxaliplatin and an immune checkpoint inhibitor. The temperature-sensitive hydrogel can form gel in situ under the triggering of body temperature, and meanwhile, the acting time of the medicine on a target part is prolonged. The antihypertensive drug losartan potassium can reduce tumor interstitial substances, reduce tumor solid stress, relieve vascular compression in tumors and improve tumor hypoxia. Meanwhile, the chemotherapeutic drug oxaliplatin can induce tumor immunogenic cell death, and the tumor immunosuppressive microenvironment is effectively relieved. The immune checkpoint inhibitor can be used for accurately blocking the combination of the PD-L1 and the PD-1 and activating the T cell mediated anti-tumor immune response. According to the present invention, the potent anti-tumor immune response can be triggered, the excellent tumor inhibition effect can be achieved, the strong far-end effect can be even induced, and the growth of the far-end tumor can be effectively inhibited.

The invention provides a marker for detecting gastric cancer immunotherapy drug resistance, application of the marker, a model and a use method of the model, provides remarkable influence of a low-oxygen tumor microenvironment on gastric cancer immunotherapy drug resistance, and highlights key effects of FOXO3a and PD-L1 expression in a mediated immune escape mechanism. An innovative microfluidic tumor chip model is adopted, the in-vivo tumor hypoxia environment is successfully simulated, and how FOXO3a up-regulation induced by the hypoxia condition causes PD-L1 expression enhancement and further causes immunotherapy drug resistance is disclosed.

The invention belongs to the technical field of microorganisms, and particularly discloses an anesthesia coating spore as well as a preparation method and application thereof. The coating spore comprises a spore and a ferric iron-propofol coating attached to the body surface of the spore, and the coating is formed through metal-phenol complexing and pi-pi stacking. The spores are dormant bodies of collagenase-producing bacteria. The coating spores can be selectively germinated and colonized in a tumor hypoxic microenvironment, Fe < 3 + > can promote bacterial proliferation, loaded propofol inhibits tumor metastasis by inhibiting migration and invasion of tumor cells, generated collagenase degrades tumor collagen, meanwhile, Fe < 3 + > is reduced into Fe < 2 + > by glutathione in the cells, and the coating spores can be selectively colonized in the tumor hypoxic microenvironment. Therefore, a powerful Fenton reaction is induced to trigger lipid peroxidation, and ferroptosis of tumor cells is initiated. The injection of the anesthetic coating spores in the single tumor not only effectively ablates the primary tumor and inhibits the growth of the tumor, but also significantly inhibits the distal pulmonary metastasis of the in-situ tumor model.

To provide tyrosine kinase inhibitors, and a method for suppressing angiogenesis, metastasis, oncogenesis, and / or immune regulation activities.SOLUTION: The present disclosure generally relates to a novel multiple target inhibitor of tyrosine kinases (TK) which can suppress angiogenesis, metastasis, oncogenesis, and / or immune regulation activities by inhibiting TK and have very potent immunomodulatory activity. The present disclosure also relates to a method of using the tyrosine kinase inhibitors, alone or in combination with HDAC inhibitor, for the treatment of cancers, in particular in cancer immunotherapy, by regulating the tumor microenvironment, including reducing tumor hypoxia, reducing lactic acid accumulation, activating CTL, inhibiting the number and activity of immunosuppressive cells, finally obtaining superior anti-cancer benefits and / or producing lasting immune memory.SELECTED DRAWING: None

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.

The application discloses a kind of nanomedicine for tumor hypoxia, which is prepared by mPEG-SS-PLGA wrapping drug IR-1048, PFOB and 4-MU.The nanomedicine of the application is constructed by wrapping perfluorooctyl bromide (PFOB), 4-methyl umbelliferone (4-MU) and IR-1048 in tumor microenvironment-responsive amphiphilic polymer mPEG-SS-PLGA, and in response to high GSH in tumor area, 4-MU, PFOB and IR-1048 are released; 4-MU makes the dense tumor extracellular matrix loose, so that tumor vessels are normalized, which is conducive to PFOB carrying oxygen into the tumor interior, long-term solution of tumor hypoxia, remodeling of tumor microenvironment, and reduction of myeloid-derived suppressor cell (MDSC) infiltration; and under the action of 980nm laser in vitro, IR-1048 responds, and the effect of photothermal therapy of tumor is improved.

The invention relates to a tumor hypoxia level evaluation model and application and a detection kit thereof, and belongs to the technical field of biomedicine. According to the scheme, a reliable breast cancer hypoxia gene set is established by using transcriptomics big data, hypoxia characteristics of clinical samples are described according to the breast cancer hypoxia gene set, hypoxia scores of the clinical samples are calculated, the relationship between the hypoxia scores of the clinical samples and clinical prognosis is explored, a prediction model with clinical application value is established, and the clinical application value of the clinical samples is predicted. And predicting the drug sensitivity according to the hypoxia score of the clinical sample. The scheme provided by the invention has important application prospects in multiple fields such as tumor treatment and drug screening.

The application provides a recombinant oncolytic virus targeting a tumor hypoxic microenvironment and an application thereof. A genome of the recombinant oncolytic virus comprises at least one nucleic acid fragment selected from a first nucleic acid fragment, a second nucleic acid fragment and a third nucleic acid fragment; wherein the first nucleic acid fragment comprises genes encoding an immunosuppression relief and T cell local activation unit and genes encoding a T cell function enhancement and chemotactic expansion unit; the second nucleic acid fragment comprises genes encoding a hypoxia sensing unit and genes encoding a T cell activation antibody expression unit; and the third nucleic acid fragment comprises at least one gene encoding an immunomodulatory unit. The recombinant oncolytic virus has three action mechanisms of a high remodeling of a solid tumor microenvironment, a universal in vivo T cell adapter and a virus conditional replication regulation, and can be effectively used for tumor treatment.

The present invention provides a bimetallic nanoassembly, a preparation method thereof, and an application thereof. The method comprises: A) mixing a phenolic polymer with a surfactant solution; B) mixing the solution obtained in step A) with a hafnium chloride solution; C) mixing the solution obtained in step B) with a cross-linking agent and a copper sulfate solution; D) adjusting the pH of the solution obtained in step C) to 7 to 9, centrifuging and precipitating, and obtaining an Hf-Cu polyphenol nanoassembly. The coordination-mediated bimetallic HfCu-polyphenol self-assembly method provided by the present invention is simple, environmentally friendly, inexpensive, and has good biocompatibility. It provides a synthesis strategy for radionuclide-labeled HfCu-bimetallic nanoassembly structures that can improve tumor hypoxia. It also provides new ideas for the diagnosis and treatment of clinical internal and external radiotherapy tumors.

The present application relates to the technical field of microorganism, specifically relates to an engineering bacteria, a construction method, an engineering bacteria medicine delivery system and purposes thereof, and provides an engineering bacteria, which comprises at least one coding gene A capable of coding interferon IFN-gamma; the chassis bacteria of the engineering bacteria is Clostridium butyricum; since Clostridium butyricum is an anaerobic gram-positive bacteria, its spores can resist adverse environment and enter the intestinal cavity through gastric juice, and in view of the hypoxic microenvironment of tumor, the engineering bacteria Clostridium butyricum spores of the present application can target the hypoxic microenvironment of tumor, and further can mildly express IFN-gamma, the expression amount is stable, and it is more safe and reliable.