67 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 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 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 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 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 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.

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 present invention provides an imaging device and method for in vivo quantitative research on tumor hypoxia. The present invention provides a rapid photoacoustic excitation light source for multispectral photoacoustic and photoacoustic lifetime imaging, and excites to form photoacoustic signals for photoacoustic imaging; constructs a magnetic field-free line and an excitation short pulse waveform, measures the concentration distribution of magnetic nanoparticles in the tumor to be measured, and realizes magnetoacoustic imaging; collects the photoacoustic signals of photoacoustic imaging and the magnetoacoustic signals of magnetoacoustic imaging to provide raw data for rapid three-dimensional reconstruction; receives the photoacoustic signals of photoacoustic imaging and the magnetoacoustic signals of magnetoacoustic imaging for photo-magnetoacoustic image reconstruction, and intelligent spectral separation and quantitative analysis of multispectral photoacoustic images. Through the present invention, the comprehensive and accurate description of tumor hypoxia characteristics is realized, the heterogeneity of tumor hypoxia in physiology and pathology is analyzed, and an accurate and reliable imaging tool is provided for the basic research of tumor hypoxia.

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 present invention discloses an amide bond-linked polyethylene glycol-phospholipid lipid-forming material with the following structural formula, its preparation method and application, belonging to the technical field of biomedical materials. The amide bond-linked polyethylene glycol-phospholipid lipid-forming material of the present invention is prepared from distearoyl phosphatidylethanolamine DSPE and PEG 2K -CDM through an acylation reaction. The amide bond-linked polyethylene glycol-phospholipid lipid-forming material of the present invention can be used to prepare nanoliposomes with the effect of alleviating tumor hypoxia. The liposomes prepared from the amide bond-linked polyethylene glycol-phospholipid lipid-forming material and biguanide cationic materials in the present invention can remove PEG in the tumor tissue matrix, promote the penetration of nanoparticles in tumors and the internalization of tumor cells, increase the drug content in tumor cells, and thus improve the drug treatment effect. #imgabs0#