40 results about "Tumor hypoxia" patented technology

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 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 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 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 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 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.

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 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 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.

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 belongs to the technical field of biological medicines, and provides a porphyrin coupled ruthenium (II) complex as well as a preparation method and application thereof. The porphyrin coupled ruthenium (II) complex (PorRu, as shown in the following formula) can be selectively enriched in tumor tissues and is highly specifically combined with G quadruplex (G4) DNA (deoxyribonucleic acid) in a double-lock mode. The dual-binding configuration of PorRu enhances the stability of the structure interacting with DNA, so that more efficient photodynamic activation is realized. When PorRu is combined with G4 DNA and exposed to near-infrared light, high-level active oxygen can be generated, guanine bases are directly oxidized to form 8-oxoguanosine damage, the oxidative damage causes mitochondrial dysfunction and induces pyroptosis, and efficient tumor inhibition is achieved through a synergistic mechanism. The PorRu provides a promising strategy for breaking through the tumor hypoxia barrier, and has huge clinical transformation potential in the field of hepatocellular carcinoma treatment.

The application discloses an FBXO48 inhibitor which can effectively enhance the curative effect of paclitaxel under lung cancer hypoxia, and particularly relates to a combined use of an FBXO48 inhibitor (BC1618) and a chemotherapeutic drug (paclitaxel) and application of the combined use in preparation of a drug for treating hypoxia-driven drug-resistant tumors. The application discloses for the first time that FBXO48 up-regulates CA9 and glycolysis pathway through a CAMKK2-pAMPK alpha-HIF1 alpha signal axis, and mediates drug resistance of tumor cells to chemotherapeutic drugs such as paclitaxel under hypoxia. The FBXO48 inhibitor (BC1618) can restore the sensitivity of tumor cells to chemotherapeutic drugs by blocking the signal axis, and shows a significant synergistic effect in patient-derived tumor organoids and mouse xenograft models. The application provides a brand-new combined treatment strategy for overcoming the chemotherapeutic resistance caused by the tumor hypoxic microenvironment.

The invention discloses a hyaluronic acid-based nano-drug, which is characterized in that hyaluronic acid is used as a carrier, cystamine dihydrochloride is used as a disulfide bond bridge, and an HC nano-carrier is prepared through an amidation reaction; then respectively covalently bonding Ce6 and glucose oxidase (GOX) to HC to obtain HCC / G nanoparticles; and carrying out in-situ growth on the surfaces of the particles through an oxidation-reduction reaction, and coating MnO2 nanosheets on the surfaces of the particles to prepare the target nano-drug. The nano-drug can respond to the characteristics of high GSH / H2O2 and weak acidity of a tumor microenvironment. Specifically, MnO2 reacts with GSH and H2O2 to generate O2, so that tumor hypoxia is relieved, and 660 nm laser mediated photodynamic therapy (PDT) is enhanced; the exposed GOX catalyzes glucose to generate H2O2, and GOx can induce glucose consumption to achieve starvation therapy (ST); generated Mn < 2 + > and H2O2 are subjected to a Fenton-like reaction, and chemical kinetic therapy (CDT) is achieved. Meanwhile, Mn < 2 + > can be used for magnetic resonance imaging, and GSH reduces disulfide bonds to release Ce6 to recover fluorescence, so that fluorescence / magnetic resonance bimodal imaging guided PDT / ST / CDT synergistic anti-tumor is realized.

The invention discloses a construction method and application of an acidic pH response bio-orthogonal cross-linked AIE nano system, the acidic pH response bio-orthogonal cross-linked AIE nano system comprises a nanoparticle 1 and a nanoparticle 2, the nanoparticle 1 is composed of PCL-PEG, PCL-PAE-DBCO and an AIE photosensitizer, and the nanoparticle 2 is composed of PCL-PEG, PCL-PAE-N3 and an AIE photosensitizer. The acidic pH response bio-orthogonal cross-linked AIE nano system has the beneficial effects that in an acidic environment (pH is 6.5), the chain length of PAE is larger than that of PEG, and the pH response bio-orthogonal cross-linked AIE nano system has the advantages that the pH response bio-orthogonal cross-linked AIE nano system has a good application prospect. The AIE photosensitizer entrapped by the nano-particles is used for effectively pushing biological orthogonal groups to the outer layers of the nano-particles, the nano-particles 1 and the nano-particles 2 are triggered to be subjected to biological orthogonal reaction and then are cross-linked together, and the AIE photosensitizer entrapped by the nano-particles not only can be used for fluorescence imaging, but also can generate I-type active oxygen to effectively tolerate tumor hypoxia, so that the effect of enhancing tumor photodynamic therapy is achieved.

The application discloses a kind of tannin-based Mn-Fe diatomic metal polyphenol nano-carrier loaded hypocrellin B nano-assemblies and its preparation method and application.The nano-assemblies use tannin as ligand, by step coordination driven self-assembly strategy, first with Mn 2+ Forming pre-assembly template, then introducing Fe 3+ Constructing Mn-Fe diatomic metal polyphenol network with atomic level uniform dispersion, and loading traditional Chinese medicine source photosensitizer hypocrellin B to obtain nano-preparation.The preparation realizes Fe 2+ / Fe 3+ Self-circulation, and can sustainably catalyze H2O2 in tumor microenvironment to generate hydroxyl radical, realizes long-acting chemical kinetics treatment;Meanwhile, in-situ oxygen production relieves tumor hypoxia, improves photodynamic therapy effect, and consumes glutathione to amplify oxidative stress.The preparation process of the application is mild, and biocompatibility is good, and it breaks through the bottleneck of insufficient effect of traditional treatment in anoxic tumor.

The application provides a kind of double drug co-loading intelligent liposome and its preparation method and purposes, belong to the field of biological medicine.The double drug co-loading intelligent liposome includes the following raw materials: curcumin, near-infrared type photosensitizer, phospholipid A, sterol compound, polyethylene glycol modified targeting lipid;The polyethylene glycol modified targeting lipid is sequentially connected by phospholipid B, responsive link, polyethylene glycol and tumor targeting ligand.The application constructs double drug co-loading liposome system with active targeting and tumor microenvironment responsiveness, forms the efficient synergistic treatment strategy of "vascular normalization+PDT", realizes drug precise delivery and enrichment, has excellent ability to inhibit tumor growth, induce tumor vascular normalization and relieve tumor hypoxia, has synergistic effect in inhibiting HIF-1 alpha expression, significantly improves the treatment effect, and provides a new scheme for efficient and safe treatment of tumor.

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 gold cluster capable of relieving tumor hypoxia and realizing photothermal and photodynamic therapy, and belongs to the crossing field of nanomaterial chemistry and biomedicine. According to the invention, fluorine-containing substance 4-trifluoromethyl thiophenol is used as a fluorine-containing protective ligand, and the atomic-scale precise gold nano-cluster with near-infrared two-zone emission characteristic is synthesized by a one-pot method. The chemical formula of the compound is C126H72Au25F54S18 (abbreviated as Au25 (CF3SPh) 18), the compound belongs to a monoclinic system, and the space group is a chiral space group P21. The nano gold cluster has a relatively small size (-2.3 nm) and good dispersity; the fluorescent probe can be excited by near-infrared light, the position of an emission peak is 1092 nm, and the fluorescent probe is suitable for near-infrared two-region fluorescence imaging of a mouse living body. The nanogold cluster material can relieve tumor hypoxia, can play a synergistic treatment role as a photothermal agent and a photosensitizer, and has efficient anti-tumor performance.

The invention discloses a liposome with synergistic oxygen release kinetics, a composition and a synergistic sonodynamic therapy system. The composition comprises at least two targeting oxygen-enriched phase change liposomes with different average particle sizes, and each liposome comprises a carrier skeleton, a sound-sensitive agent, a carbon perfluoride ultrasonic response phase change agent encapsulated inside and loading oxygen, and a targeting ligand modified on the surface. Liposomes with different particle sizes can be obtained by controlling the ultrasonication time in the preparation process. On the basis of the Laplace pressure difference principle, liposomes with different particle sizes have different phase change thresholds under the same ultrasonic condition, so that the liposomes can sequentially generate phase change and release oxygen according to a time sequence under therapeutic ultrasonic irradiation, and continuous and controllable oxygen supply is realized. The composition can form a synergistic treatment system with an ultrasonic generation device, released oxygen serves as a substrate for reaction of a sound-sensitive agent, tumor hypoxia is effectively relieved, generation of active oxygen is remarkably enhanced, and the sonodynamic treatment effect is improved.

The invention discloses a preparation method and application of a cascade nanoreactor based on a near-infrared II-region type-I photosensitizer, and relates to the technical field of biomedicine. Through the molecular design of the near-infrared II-region I-type photosensitizer, the near-infrared II-region I-type photosensitizer has excellent near-infrared II-region fluorescence performance, efficient photothermal conversion capacity and strong active oxygen generation capacity, and functional stability is enhanced by means of aggregation-induced emission characteristics; according to a cascade nano reactor constructed based on the photosensitizer, tumor targeted enrichment is achieved by means of appropriate particle sizes, efficient killing components are generated in situ through a cascade reaction of a light-triggered I-type photodynamic effect and heat-activated nitric oxide release, photo-thermal, photodynamic and gas treatment effects are synergistically exerted, meanwhile, a near-infrared II-region imaging function is integrated, and tumor targeted enrichment is achieved. Diagnosis and treatment integration is realized; the system can effectively overcome the obstacles of tumor hypoxia and abundant matrixes, improves the treatment accuracy and effect through multi-mechanism cooperation, and provides an innovative strategy for accurate tumor treatment.

The invention relates to the technical field of drug delivery systems, in particular to a dual-targeting micro-nano robot based on probiotics and framework nucleic acid and a preparation method of the dual-targeting micro-nano robot. In the invention, a drug is introduced into an ECN engineering bacterium (ECN-pl) capable of sensing tumor hypoxia microenvironment lysis as a delivery strategy, so that the activity resistance caused by surface modification to the strain can be avoided; after the DOX (at) FDN-A2.2 (at) ECN-pl enters a body, the DOX (at) FDN-A2.2 (at) ECN-pl goes deep into a tumor core and senses hypoxia of tumor cells to generate cleavage protein and destroy an ECN structure, so that the DOX (at) FDN-A2.2 is successfully released to the tumor core; wherein AS1411 and S2.2 aptamers on the surface of the FDN-A2.2 have the capability of targeting tumor cells, so that the uptake rate of the tumor cells is increased by the dual-targeting aptamers on the surface of the FDN-A2.2; the problem of tumor drug resistance is solved, so that the growth of tumor cells is inhibited.

The application belongs to the technical field of biological medicine and photodynamic therapy, and particularly relates to an aggregation-induced emission photosensitizer with tumor hypoxia relief function and a preparation method and application thereof. The photosensitizer is MeTCP-F, which uses methoxy-modified triphenylamine as an electron donor, benzindole as an electron acceptor, and thiophene as a pi bridge to form a D-pi-A structure, and is connected with a perfluorinated compound through an ester bond; and the MeTCP-F NPs are prepared by using CH3-PEG-DSPE through a nano precipitation method. The photosensitizer has near-infrared fluorescence imaging, active oxygen generation and oxygen carrying capacity, can relieve tumor hypoxia, cooperatively realize the generation of type I and type II active oxygen, and improve the photodynamic therapy effect. The MeTCP-F NPs have good water solubility and high biocompatibility, can be enriched in tumor tissues through the EPR effect, can realize efficient tumor killing under the guidance of near-infrared imaging, have low systemic toxicity, and have application value in the preparation of anti-tumor photodynamic therapy drugs.

The application discloses a near-infrared fluorescence and photoacoustic dual-mode small molecule probe activated by nitroreductase, which can be activated by nitroreductase to be converted into a compound with fluorescence and photoacoustic signals, and a compound structure general formula of the small molecule probe is shown in the following formula: wherein R can be substituted at 4, 5, 6 and 7 positions, and the substituent group is one of H, OCH3, F and Cl; the small molecule probe compound itself has no fluorescence and photoacoustic; under catalysis of nitroreductase, the nitro group is reduced to an amino group to be converted into a compound integrating optical imaging and photoacoustic imaging, therefore, the small molecule probe is applied to tumor hypoxia imaging, near-infrared fluorescence and photoacoustic dual-mode can be simultaneously started only by activation of nitroreductase in tumor cells, and high specificity, high resolution, high sensitivity and high penetration depth imaging of the tumor can be realized.

The invention relates to the technical field of nano material preparation and biological medicine, and discloses a composite preparation for co-delivery of a photosensitizer and catalase and a preparation method thereof.The composite preparation comprises a patch substrate, microneedles arranged on the patch substrate and nanoparticles dispersed in the microneedles, the nanoparticles comprise catalase and a hydrophobic photosensitizer loaded on the catalase in situ. The MN patch can realize targeted co-delivery of PS and CAT, and under the triggering of a tumor acidic microenvironment, NPs are controllably degraded, the enzyme activity of CAT is recovered, and PS is synchronously released. The released CAT efficiently catalyzes the overexpressed H2O2 in the TME to generate O2, so that the tumor hypoxia is relieved, and the PDT curative effect is enhanced; and meanwhile, an acid response'closing-opening 'mechanism avoids early release damage of PS to normal tissues. The double limitations of low PS delivery efficiency and tumor hypoxia in traditional PDT are broken through, and an integrated solution is provided for solid tumor treatment.