89 results about "Metabolic reprogramming" patented technology

The invention relates to an in vitro method for classifying a subject afflicted with a cancer as suffering from a cancer with (at risk of) a metabolic reprograming towards fatty acids oxidation including a step of assaying the activation of RelB in a tumor sample form said cancer. The inventor indeed identified the pivotal role of RelB in energy metabolism and more particularly mitochondrial respiration and fatty acid oxidation. Accordingly, the invention also relates to inhibitors of RelB activity or expression, as well as of lipid metabolism for use in the treatment of cancers showing an activated RelB.

The invention relates to the technical field of biological medicine, and discloses a culture medium for human metapneumovirus and application, the culture medium comprises the following components by mass: 850-920 parts of a basic culture medium; the metabolism reprogramming module is prepared from the following components in parts by weight: 0.05 to 0.15 part of 5-methyltetrahydrofolic acid, 0.3 to 0.7 part of N-acetyl-D-mannosamine and 1.0 to 3.0 parts of sodium dichloroacetate; the immune regulation and control module is prepared from 0.005 to 0.015 part of an RIG-I / MAVS pathway inhibitor; the receptor induction module is prepared from 0.5 to 1.5 parts of all-trans retinoic acid; the redox balance module is prepared from the following components in parts by weight: 0.1 to 0.5 part of pegylated superoxide dismutase and 0.002 to 0.008 part of sodium selenite. According to the method, the proportion of infectious virus particles can be remarkably increased, the generation of defective particles is reduced, meanwhile, the production cycle of host cells is prolonged, large-scale continuous culture is supported, and a high-quality and high-efficiency solution is provided for industrial production of gene therapy vectors and virus vaccines.

The invention discloses an application of nicotinamide adenine dinucleotide in preparation of a medicine for treating keloid, and by researching the pathophysiological mechanism of keloid, it is found that mechanical related fibroblasts of keloid patients have metabolic reprogramming changes. Fibroblast populations which are mainly pathogenic to keloid have metabolic reprogramming caused by mitochondrial dysfunction, especially glycolysis level enhancement in cells and lactic acid accumulation. The medicine, namely NAD +, capable of regulating and controlling keloid fibroblast glycolysis and mitochondrial metabolism is found and verified through cell and animal experiments, and NAD + inhibits development of keloid by improving mitochondrial dysfunction, reducing lactic acid accumulation and inhibiting fibroblast migration and collagen synthesis. According to the invention, NAD +, which is a common medicine with good safety, is applied to keloid for the first time, and the scheme has small toxic and side effects and also has positive effects on oxidation resistance, aging resistance and cancer resistance, so that a new scheme is provided for treating keloid by medicines.

The invention relates to the technical field of osteoarthritis drugs, particularly discloses an application of DDX5-K45mRNA in preparation of drugs for treating and / or relieving osteoarthritis, and provides a drug delivery system for targeting chondrocytes at the same time, research finds that when DDX5-K45mRNA is added into the chondrocytes, the drug delivery system can be used for treating and / or relieving osteoarthritis. The medicine can restore DDX5-K45 lactic acid, block NF-kappa B inflammation signals, correct metabolic reprogramming (such as inhibition of abnormal glycolysis), and up-regulate cartilage protection factors such as COL2A1 and the like. The LNP is utilized to efficiently deliver DDX5-K45mRNA to cartilage cells, endogenous lactic acid modification defects are directly supplemented, the cartilage protection function of DDX5 is reconstructed, inflammatory response is inhibited, matrix degradation is reduced, the cartilage steady state is maintained fundamentally, and long-acting and safe OA treatment is achieved.

The invention discloses application of sorafenib in maintenance treatment of acute myelogenous leukemia after transplantation, and relates to the technical field of medicines, and the key points of the technical scheme are as follows: it is found for the first time that secretion and killing functions of NK cells can be enhanced by using sorafenib for maintenance treatment after transplantation; sorafenib enhances communication between macrophages and NK cells by promoting secretion of macrophage proinflammatory factors, so that the function of NK cells is enhanced. The invention clarifies that sorafenib enhances the GVL effect of NK cells in a low tumor load environment, discusses the molecular mechanism of sorafenib for enhancing the NK cell function by promoting macrophage metabolism reprogramming, and provides a new thought for maintaining precision and optimization of treatment after transplantation.

The invention discloses an application of a DHA-RXR-PPAR signal channel in promotion of postoperative recovery of hysteromyoma after HIFU (high intensity focused ultrasound). Clinical sample metabolic spectrum analysis and in-vitro cell function experiments are combined, and research proves that the differential metabolite DHA drives macrophage metabolism reprogramming through an RXR-PPAR signal axis, so that the macrophage is promoted to be transformed into an anti-inflammatory and phagocytosis-promoting repair phenotype, the absorption and repair process of the HIFU postoperative hysteromyoma is accelerated, and the treatment effect of the HIFU postoperative hysteromyoma is improved. A new intervention target spot (RXR-PPAR gamma axis) and a new potential medicine are provided for HIFU (high intensity focused ultrasound) postoperative rehabilitation.

The invention discloses a method and device suitable for tumor glucose metabolism reprogramming driving factor analysis, and the method comprises the steps: generating a gene expression matrix for a biological pathway under a sample; performing dimension reduction processing on the gene expression matrix to obtain a first low-dimensional representation and a second low-dimensional representation; inputting the first low-dimensional representation and the second low-dimensional representation into a causal direction inference structure, and outputting a plurality of initial causal direction inference results; selecting from the plurality of initial causal direction inference results to obtain a target causal direction inference result corresponding to the sample; and finally, analyzing and comparing a target causal direction inference result under a normal sample and a target causal direction inference result under a tumor sample to obtain an analysis result, and indicating that Fenton reaction in cells drives tumor glucose metabolism reprogramming. Therefore, key factors of tumor glucose metabolism reprogramming can be quickly and accurately identified, and the fact that the Fenton reaction in cells is a main reason of tumor glucose glycolipid metabolism reprogramming is found.

The present invention discloses the application of the PPP1R3B gene in the preparation of atherosclerotic detection reagents or therapeutic drugs. The present invention for the first time discovers that the PPP1R3B gene is a reliable target for the diagnosis and treatment of atherosclerosis. By exogenous up-regulation of the expression of PPP1R3B, inducing the polarization of M2-type MΦ macrophages, it can alleviate the plaque inflammatory microenvironment, promote glycolipid metabolic reprogramming, support the energy load required by cells, delay the progression of atherosclerotic plaques, improve the quality of life of cardiovascular disease patients, reduce the incidence of cardiovascular and cerebrovascular events, and can be applied to the preparation of atherosclerotic diagnostic reagents and therapeutic drugs.

The invention discloses a polyphosphate-metal nano-composite as well as a preparation method and application thereof, and belongs to the technical field of biological medicines and nano-materials. The polyphosphate-metal nano-composite is formed by self-assembly of polyphosphate and metal ions under the coordination action; wherein the chain length of the polyphosphate is 20 to 75. According to the invention, divalent metal ions are introduced, so that polyphosphate and metal ions form a spherical nano-composite through coordination self-assembly, the composite can be absorbed by tumor cells and degraded under an acidic condition, released polyphosphoric acid is separated through unique Ca < 2 + > phase, Ca < 2 + > is enriched around mitochondria, and the function of tumor treatment is realized. And tumor cell metabolism reprogramming is caused to be dominated by oxidative phosphorylation, so that copper death and immunoregulation are induced, and a triple synergistic anti-tumor effect is realized.

The invention discloses application of a PAPSS2 inhibitor in preparation of a medicine for treating bladder cancer. Based on the principle that PAPSS2 inhibits p53 expression through sulfurylation modification and mediates purine metabolism reprogramming to promote bladder cancer progress, a sulfurylation rate-limiting enzyme PAPSS2 is used as a core target spot for bladder cancer treatment, the target spot is a key upstream molecule for regulating purine metabolism reprogramming, and high expression of the target spot is directly related to poor prognosis of bladder cancer; the PAPSS2 inhibitor is adopted to specifically inhibit expression or activity of PAPSS2, so that the pathway is intervened to block a metabolic reprogramming process of bladder cancer, and the core is to inhibit PAPSS2-mediated p53 sulfurylation modification and recover an inhibition function of p53 on purine metabolism. According to the invention, the feasibility and effectiveness of bladder cancer metabolism targeted therapy are obviously improved.

This invention discloses an immune cell that secretes type 2 cytokines under hypoxic conditions and its applications, belonging to the fields of genetic engineering and cell engineering. The invention first constructs a nucleotide fragment encoding hypoxia-induced type 2 cytokines, including a signal peptide gene sequence, a CAR molecule nucleotide sequence targeting CD19 and CD22, and an IL-4 or IL-10 nucleotide sequence containing multiple HRE motifs of a hypoxia-inducible promoter. This nucleotide fragment is delivered to immune cells for stable expression, yielding an immune cell that secretes type 2 cytokines under hypoxic conditions. This immune cell secretes IL-4 or IL-10 only under hypoxic conditions, thereby leveraging the metabolic reprogramming effect of IL-4 or IL-10 on immune cells to enhance their activity under hypoxic conditions, thus achieving better long-term anti-tumor effects.

The invention discloses a nucleolin aptamer modified carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system as well as a preparation method and application thereof, and relates to the field of tumor treatment. The nucleolin aptamer AS1411 is coupled with glycolysis regulation nano-particles through covalent bonds, and the carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system comprises a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system and a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, the glycolysis regulation nano-particles take carboxymethyl chitosan as a carrier skeleton, the carrier skeleton is loaded with a lonidamine derivative through grafting modification, and the nano drug delivery system can synchronously entrap paclitaxel. According to the invention, a synergistic treatment system integrating active targeting, metabolic regulation and chemotherapy is constructed, and by virtue of a multi-mechanism synergistic effect, an antitumor drug for inhibiting tumor cell activity, glycolysis or tumor metabolism reprogramming is prepared; the huge potentials of overcoming the drug resistance bottleneck of traditional chemotherapy, enhancing the curative effect and reducing the toxic and side effects are shown.

The invention discloses double-response hydrogel as well as a preparation method and application thereof. The double-response hydrogel comprises a three-dimensional porous network hydrogel matrix, and tea polyphenol and nano silicon nitride which are loaded in the hydrogel matrix, the three-dimensional porous network hydrogel matrix is prepared from o-nitrobenzene grafted hyaluronic acid and carboxyl phenylboronic acid modified methyl chitosan. According to the hydrogel disclosed by the invention, in a low-pH / high-ROS microenvironment of a diabetic periodontitis focus, boric acid ester bonds are broken, tea polyphenol is released, and the tea polyphenol plays an anti-inflammatory role by efficiently removing active oxygen and inhibiting inflammatory factors; meanwhile, the Schiff base bond is dissociated to release the nano silicon nitride, and the nano silicon nitride significantly promotes angiogenesis and osteogenic differentiation and accelerates bone defect repair by activating a redox signal, inducing cell autophagy, regulating metabolic reprogramming and other pathways.

The invention relates to the technical field of biological medicine, and particularly discloses a macrophage membrane coated plateau encephaledema drug carrier and a preparation method and application thereof, and the macrophage membrane coated plateau encephaledema drug carrier is composed of a nanoparticle core and a macrophage membrane shell layer wrapping the core; the nanoparticle core comprises an ROS-responsive carrier material and carbon monoxide release molecules MnCO entrapped in the ROS-responsive carrier material; the content of phosphatidylserine in the shell layer of the macrophage membrane is not less than 5 mol% of the total phospholipid of the membrane. According to the invention, a bionic delivery system of ROS response type MnCO nanoparticles coated with a macrophage membrane is constructed, phosphatidylserine on the surface of the membrane is utilized to actively activate a microglial cell Trem2 receptor, a positive feedback cycle of targeting phagocytosis-CO release-Trem2 up-regulation is formed, and at the same time, fatty acid oxidative metabolism reprogramming is promoted by means of degraded membrane lipid, so that the biomimetic delivery system is used for preparing the ROS response type MnCO nanoparticles. And multi-mechanism synergistic efficient brain-targeted therapy is realized.

T lymphocytes play a key role in the immune response and their functions are intimately linked to metabolic programs. During immune responses, T cells undergo a metabolic reprogramming notably characterized by an increased aerobic glycolysis. Using a quantitative phosphoproteomic approach, the inventors have identified a new transcription factor called Foxk1 as being highly phosphorylated in T cells upon T Cell Receptor (TCR) engagement. The results also indicate that Foxk1 phosphorylation and nuclear translocation is dependent of the AKT-mTOR kinase activities. Using T-cell specific Foxk1 deficient mice (Foxk1- / -), we demonstrated that Foxk1 is required for full T cell activation. Foxk1-deficient T cells exhibited reduced proliferation and cytokine secretion following TCR stimulation. Furthermore, T cells from Foxk1- / - mice were less prone to acquire an effector like phenotype than wild-type cells when challenged in vivo. Conversely, Foxk1 overexpression in T cells enhanced their effector functions in a TCR-dependent manner. In CD8+ T cells, this effect also results into enhanced cancer cell killing capacity in vitro, and improved tumor rejection in vivo. Altogether, these results indicated that Foxk1 is a major regulator of T cell metabolism and thus, of T cell effector functions. Thus, the present invention relates to host immune cells engineered to overexpress a Foxk1 polypeptide and their use of the treatment of cancer.

The application discloses a kind of biological hybrid micro machine population oral delivery system of imitating Helicobacter pylori survival mechanism, belong to oral stomach medicine delivery technical field.The system is by active power module (flagellum driven chlamydomonas reinhardtii), environmental regulation module (acid urease modified on algal surface) and multifunctional load module (macrophage membrane wrapped drug-loaded nanoparticles) synergistic assembly through polydopamine (PDA) spatial conformation control layer is formed.Active power module utilizes self-movement ability to penetrate mucus barrier and extend intracavity retention time to 12 hours or more;Environmental regulation module produces local alkalization effect by catalyzing urea hydrolysis, provides chemical shield for system in extremely acid environment of pH 1.0-3.0, protects active power module from gastric acid inactivation;Multifunctional load module is accurately delivered to gastric epithelial cells by inflammation targeting effect, such as CRISPR / Cas9 biological macromolecule, and realizes up to 31.8% in-vivo gene editing efficiency.The application provides a non-invasive, modular active delivery platform for the precise treatment of gastric diseases such as gastritis through the synergistic effect of physical penetration, metabolic reprogramming and gene intervention.

The invention relates to the technical field of biological medicines, in particular to application of arbidol in preparation of antitumor drugs. The invention provides an application of arbidol in preparation of antitumor drugs. Umifenovir not only can directly kill tumors by regulating metabolic reprogramming, but also can enhance immune response by regulating activation and proliferation of lymphocytes, and can remarkably inhibit expression of various cell factors. Therefore, the Umifenovir has important potential value in the aspects of improving the chemotherapy curative effect, improving the inhibitory immune microenvironment, improving the immunotherapy effect and preventing and treating common adverse reactions such as the cytokine release syndrome in immunotherapy no matter the Umifenovir is used as an independent anti-tumor drug.

The invention belongs to the technical field of microorganisms, and discloses an amorphophallus bulbifer southern blight infection influence analysis method based on metabonomics and microbiomics. Conjoint analysis shows that core florae (such as Streptomyces, Penicillium and Bauldia) are in significant positive correlation with phenylpropanoids and glutathione (succinic acid, coniferyl alcohol and glutamic acid), succinic acid is in positive correlation with Kribbella and Terrimonas, 2 ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', 2' ', the 3, 3 '-cycle CMP is negatively correlated with pathogen-related bacteria, which indicates that the metabolite regulates and controls the abundance of specific bacteria through positive / negative feedback so as to drive the microecological balance of rhizosphere, and a collaborative defense strategy that plants recruit beneficial microorganisms and inhibit pathogenic bacteria through metabolism reprogramming is disclosed.

The present invention provides a liposome, a preparation method thereof, and an application thereof in the preparation of a drug for treating PARP inhibitor-resistant breast cancer, relating to the field of biotechnology. A preparation method of a liposome provided by the present invention includes: injecting an ethanol solution dissolved with soybean phospholipid and cholesterol into an aqueous histidine solution for hydration under stirring conditions, volatilizing the ethanol component after the hydration ends, and then preparing the liposome after ultrasonic treatment. This preparation method is simple and convenient, and the encapsulation efficiency of the prepared liposome loaded with histidine is high. Through research by the inventor, it is found that histidine metabolic reprogramming occurs during the process of PARPi resistance in breast cancer cells, enabling the maintenance of DNA synthesis and repair. After treating PARPi-resistant breast cancer cells with the liposome of the present invention, the histidine content in breast cancer cells can be increased, making PARPi-resistant cells sensitive to PARPi, thereby realizing the treatment of PARPi-resistant breast cancer.

The invention belongs to the technical field of biological medicines, and particularly relates to a novel application for regulating and controlling de-lactation acylation of a K309 site of an autophagy-associated protein 7 (ATG7) based on a silent information regulatory factor 1 (Sirt1) activator and treating tumors through targeted metabolism reprogramming. The key effect of lactoacylation modification of the K309 site of ATG7 in tumor cell metabolism reprogramming is disclosed for the first time, and it is proved that a Sirt1 activator inhibits the Warburg effect through lactoacylation, enhances mitochondrial oxidative phosphorylation (OXPHOS) and triggers metabolic stress and tumor cell death. Cell experiments prove that the Sirt1 activator has a remarkable killing effect on tumor cells with high ATG7-K309 lactoacylation level, and a new strategy is provided for precise treatment.

The application discloses a kind of for sensitizing lung cancer radiotherapy biomimetic nano delivery system and preparation method and application, it belongs to the field of biological medicine, wherein, biomimetic nano delivery system is core-shell structure, including core and the shell of the core outer layer being wrapped;Wherein, core is the lipid nanoparticle of therapeutic nucleic acid being loaded;Shell is tumor cell membrane vesicle;Therapeutic nucleic acid is the short hairpin RNA expression plasmid of targeted deubiquitinating enzyme CYLD gene.The application solves lung cancer radiotherapy resistance problem from mechanism, by therapeutic nucleic acid specific knockdown deubiquitinating enzyme CYLD gene, effectively blocks CYLD / NRP1 signal shaft, to reverse the metabolic reprogramming of tumor cell, significantly enhance its radiotherapy sensitivity, realize to the low-toxicity treatment of radiation resistance lung cancer.

The invention discloses application of a substance for reducing MMACHC expression in preparation of antitumor drugs, and relates to the field of molecular biology. The application discovers that MMACHC can regulate and control a metabolism reprogramming pathway of lipid metabolism under tumor conditions for the first time, and knockout of MMACHC can effectively inhibit the lipid metabolism pathway, so that proliferation and invasion of colorectal cancer cells are inhibited, and the development process of tumors is delayed; therefore, the MMACHC is used as a target spot for anti-tumor treatment, and the substance for reducing the expression of the MMACHC is used for preparing the anti-tumor medicine, so that the MMACHC has important significance on comprehensive treatment of tumors.

The invention discloses a bionic hybrid nano regulator for enhancing cell copper death and a preparation method and application thereof, and belongs to the technical field of biomedical materials. The invention designs a bionic nano-platform which simultaneously loads a lactic acid regulator cyclostilbene Su 3118 and a copper ion carrier disulfiram DSF, and the bionic nano-platform is combined with hybrid macrophages and tumor cell membranes to construct a nano-regulator SCTDM. The nano regulator can exert multiple functions, including tumor targeting, in-situ photothermal therapy, lactic acid regulation and enhanced copper death. The nano regulator provided by the invention is simple and convenient to manufacture, is combined with in-situ photothermal therapy and lactic acid regulation and is used for enhancing cell death immunotherapy of copper death so as to eliminate primary tumors and delay relapse, and a technical support is provided for regulating immunity by enhancing copper-induced cell death through metabolic reprogramming.

The invention relates to the technical field of pharmaceutical preparations, in particular to mRNA (messenger ribonucleic acid) lipid nanoparticles and application thereof in treatment of triple-negative breast cancer. The invention constructs an mRNA lipid nanoparticle, breaks through the dilemma of single drug curative effect of a glucose transporter (GLUT) inhibitor and a glutaminase (GLS) inhibitor for triple negative breast cancer, and realizes double-track treatment of mRNA metabolism reprogramming and small molecule energy deprivation for the first time. The mRNA lipid nanoparticles enhance the sensitivity of triple negative breast cancer to small molecule energy deprivation treatment, so that the clinical transformation feasibility of BAY-876 and CB-839 is improved to a new dimension. The delivery efficiency of the mRNA lipid nanoparticles is high, the biological safety is good, meanwhile, the production process of the nanoparticles is simpler and more standard compared with plasmids and viruses, and the drug production cost is lower.

The invention relates to application of theaflavin as a UGP2 inhibitor and application of theaflavin in preparation of a medicine for preventing and / or treating hepatocellular carcinoma, and belongs to the technical field of biology. According to the invention, the monomeric compound theaflavin derived from a natural product can be used as a UGP2 direct targeting inhibitor for the first time, and is used for preparing a liver cancer treatment medicine for regulating and controlling glucose metabolism reprogramming. The theaflavin can be specifically and directly combined at a UGP2 active site in a targeting manner through high activity to inhibit the activity of the UGP2, is the first specific inhibitor which takes the UGP2 as a target spot and is reported at present, and can be used for remarkably inhibiting tumor phenotypes such as proliferation, migration and invasion of liver cancer cells by inhibiting UGP2-mediated UDPG synthesis and intracellular glycogen accumulation.

The invention discloses a multi-source vegetable outer vesicle composition as well as a preparation method and application thereof. The multi-source vegetable outer vesicle composition is prepared from outer vesicles extracted from spinach leaves, ginger tubers, broccoli buds, bitter gourd fruits and celery stems. The spinach leaves, the ginger tubers, the broccoli flower buds, the bitter gourd fruits and the celery stems are mixed according to the fresh weight ratio of (3-5): (1-2): (2-3): (1-1.5): (2-4), and low-temperature homogenization, centrifugation and ultrafiltration purification are performed to obtain the spinach-ginger-containing beverage. The particle size of the multisource vegetable outer vesicle composition is 100-200 nm, and the multisource vegetable outer vesicle composition comprises transmembrane protein TET8 and membrane anchoring protein ANNEXIN, and further comprises active ingredients of miR159a, miR166a, quercetin and kaempferol. The outer vesicle can target a PPAR gamma / FAS pathway and regulate and control lipolysis and metabolism reprogramming of fat cells; meanwhile, an Nrf2 pathway is activated, free radicals are removed, oxidative stress injury is inhibited, and metabolic diseases such as obesity, type II diabetes mellitus and non-alcoholic fatty liver disease can be effectively improved.

The invention provides application of combination of an mTOR inhibitor and an EPAS1 inhibitor in preparation of a medicine for treating myeloproliferative tumors, through combined use of the mTOR inhibitor everolimus and the EPAS1 inhibitor PT2385, JAK2V617F mutation-driven metabolic disorder is targeted, metabolic reprogramming is effectively reversed (the lactic acid level is reduced, the alpha-ketoglutaric acid level is increased, and the lactic acid / alpha-KG ratio is corrected), and the treatment effect on myeloproliferative tumors is improved. The JAK inhibitor can be used for treating MPN, synergistically relieving splenomegaly, reversing myelofibrosis and reducing mutation allele load, the curative effect is remarkably superior to that of existing JAK inhibitor single-drug treatment, and an innovative scheme with disease modification potential is provided for MPN.

The invention provides application of pentenedioic acid (GC) in enhancing the anti-tumor effect of T cells through metabolic reprogramming, and belongs to the technical field of biological medicine. It is found that in the tumor development process, GC is supplemented in an exogenous mode, tumor growth can be rapidly inhibited, and the anti-tumor effect depends on a TME regulation and control mechanism. Through GC treatment, the TME immune landscape can be significantly remodeled; gC treatment not only can enhance the effector function of the CD8 + T cells, but also can delay the depletion process of the CD8 + T cells; and the infiltration CD8 + T cells in the tumor of the GC treatment group are obviously increased. Particularly, after the CD8-resistant antibody is used for removing mouse CD8 + T cells, the anti-tumor effect of GC completely disappears, and it is confirmed that the tumor inhibition effect depends on the CD8 + T cells. Therefore, the invention proves that the lysine catabolic metabolite GC, as an immunostimulatory metabolite, can shape the immune activated TME by reactivating the functions of tumor infiltrating CD8 + T cells.

The invention relates to the technical field of biology, in particular to an in-vivo editing and metabolism reprogramming nano drug-loaded material for targeting macrophages as well as a preparation method and application of the in-vivo editing and metabolism reprogramming nano drug-loaded material. On the basis of a metal organic framework (MOF) material, CAR mRNA molecules targeting DLL3 are loaded in the MOF material, a macrophage-derived cell membrane is coated outside the MOF material, and the nano drug-loading material with the macrophage targeting capability is constructed. The material has the effects of specifically swallowing and killing tumor cells, improves the immunosuppression effect of a tumor microenvironment by utilizing the immune activation effects of succinic acid and manganese, and synergistically promotes the killing effect on small cell lung cancer. The macrophage in-vivo editing technology designed by the invention is a novel safe, efficient, simple and convenient tumor immunotherapy technology, overcomes the defect that CAR-T cannot enter the interior of a solid tumor, and solves the problem of tedious cell in-vitro amplification and gene editing procedures in the conventional CAR immunotherapy process; and a new strategy is provided for immunotherapy of small cell lung cancer with limited treatment means.

This invention discloses a metabolically enhanced anti-tumor CAR-M cell co-expressing SLC protein, comprising the nucleotide sequence encoding the HER2 antigen-binding domain scFv and the nucleotide sequence encoding the SLC protein. The invention also discloses a method for constructing the aforementioned anti-tumor CAR-M cell and its application in the preparation of anti-tumor drugs. The anti-tumor CAR-M cell of this invention specifically recognizes HER2, thereby effectively reducing off-target toxicity, improving treatment safety and tumor specificity, and exhibiting significantly enhanced glutamine uptake capacity. It possesses a good metabolic reprogramming effect at the molecular level, resulting in stronger anti-tumor activity due to enhanced metabolism.