162 results about "Antitumor therapy" patented technology

The invention discloses an MOF-CQD enzyme-sensitive FRET hydrogel diagnosis and treatment probe as well as a preparation method and application thereof, and belongs to the technical field of biomedical detection and treatment. The probe takes a carboxyl carbon quantum dot (CQD) as a donor and a metal organic framework (MOF) as an acceptor, and the donor and the acceptor are connected through a replaceable enzyme response polypeptide bridge; when the fluorescence is complete, FRET is generated to quench the CQD fluorescence, the FRET is interrupted after the target enzyme cuts off the peptide bridge, and the blue / red fluorescence ratio is changed to realize nanomole-level quantitative detection and has self-correction capability. The probe is packaged in a four-arm PEG transparent hydrogel which does not need a photoinitiator and can be quickly self-crosslinked, and can be prepared into a film, a tooth socket and the like for POCT (point-of-care testing) of parts such as an oral cavity / skin and the like. After detection, the MOF is activated by illumination of 630-660 nm to generate active singlet oxygen, so that local antibacterial or anti-tumor treatment is realized, and a diagnosis and treatment integrated scheme is constructed.

The present invention belongs to the technical field of cancer immunotherapy, and particularly relates to a cholesterol-modified cationic liposome tumor vaccine, a preparation method therefor, and use thereof. In order to solve the problems of poor targeting and strong side effects of TLR agonists in anti-tumor treatment, the present invention provides a cationic liposome prepared from a cholesterol-modified 1V209 molecule, a cationic lipid component, cholesterol, and DSPE-PEG2000, and then the cationic liposome and ovalbumin 5 form the tumor vaccine by electrostatic adsorption. Animal experiments show that the vaccine can induce antigen-specific CD8+ T cells, activate lymphocytes, and generate stronger antigen cross-presentation, more memory T cells, antibodies, and cytokines. Prophylactic inoculation with the vaccine can significantly delay the progression of mouse melanoma and lymphoma and prolong the survival of mice. The combination use of the vaccine and a PD-1 checkpoint inhibitor can further enhance the anti-tumor effect. Therefore, the vaccine is a promising cancer vaccine.

The invention belongs to the technical field of medicinal chemistry, and particularly relates to a dammarane sapogenin-isatin derivative and application thereof in anti-tumor treatment. The dammarane sapogenin-isatin conjugate is constructed by taking dammarane sapogenin as a mother nucleus, deriving the dammarane sapogenin and chloroacetic acid and then introducing an indolone structural unit, and R1, R2 and R3 are as described in the claims and the specification. According to the invention, isatin fragments and ginsenoside are coupled for the first time, the anti-tumor activity of the compounds is systematically evaluated, and the action mechanism research of the compounds in colorectal cancer and other tumors is further developed. Results show that the obtained compound has relatively good anti-tumor efficacy, tumor cell selectivity, relatively low toxicity and relatively high bioavailability, and shows good patent medicine potential and wide market prospects.

The invention relates to the technical field of traditional Chinese medicine processing, and discloses traditional Chinese medicine processing equipment for traditional Chinese medicine anti-tumor treatment, which comprises a crushing box, the front surface of the crushing box is fixedly connected with a first motor, the output end of the first motor is provided with crushing rollers through a coupler, and the two crushing rollers are meshed with each other through a gear set; a screen is arranged in the smashing box, a suction opening of the smashing box synchronously moves along with the carding component through a suction fan and a conveying pipe, large particles which cannot pass through the screen on the screen face can be accurately and efficiently sucked up in time, and the large particles are conveyed to the top of the smashing box again through the conveying pipe and fall into the position between the two smashing rollers to be smashed again forcibly. The trouble that traditional equipment needs to be shut down to manually return materials is avoided, the materials are smashed multiple times in the single machining process, the smashing efficiency is remarkably improved, the carding plate horizontally reciprocates above the screen, large-particle materials are continuously carded, cut and smashed, and screen holes are effectively prevented from being blocked.

The invention belongs to the technical field of biomedical materials, and discloses pH-responsive injectable hydrogel as well as a preparation method and application thereof. Comprising the following steps: (1) dissolving sodium alginate in water to form a uniform solution; (2) adding a fat-soluble small molecule drug and Fe3O4 nanoparticles into the solution, carrying out high-speed shearing dispersion under an ice-water bath condition to form a drug / nano composite system, and standing; and (3) sequentially adding a calcium carbonate suspension and glucolactone into the drug / nano composite system, uniformly stirring, and incubating until the mixture is completely cured to obtain the pH-responsive injectable hydrogel. The hydrogel obtained by the invention not only has excellent injectability and pH response release performance, but also can remarkably improve the loading efficiency of fat-soluble drugs, and provides a new technical approach for realizing local anti-tumor treatment.

The invention belongs to the technical field of nano materials and anti-tumor treatment medicines, and discloses cordyceps sinensis mycelium polysaccharide-copper selenide with dual effects of inducing tumor cell apoptosis and copper death as well as a preparation method and application thereof. The preparation method of the cordyceps sinensis mycelium polysaccharide-copper selenide comprises the following steps: taking cordyceps sinensis mycelium polysaccharide as a template, adopting a soft template method, reducing Na2SeO3 through Vc, and adding CuSO4 to prepare the cordyceps sinensis mycelium polysaccharide-copper selenide. The cordyceps sinensis mycelium polysaccharide-copper selenide can selectively kill tumor cells and induce apoptosis and copper death of the tumor cells at the same time, and has huge application potential in the aspect of tumor prevention and treatment.

This application discloses a purino[1,2-a]carbazolin derivative, its preparation method, and its application. Specifically, it discloses a compound having the structure shown in Formula I, or its stereoisomers, solvates, metabolites, pharmaceutically acceptable salts, cocrystals, or prodrugs: ; wherein R1 and R2 are each independently selected from hydrogen, hydroxyl, carboxyl, substituted or unsubstituted C1-C6 alkyl, -CONH-R3, and -COO-R4; wherein R3 is a substituted or unsubstituted C1-C5 alkyl, and the substituent can be any of cyano, halogen, alkylC1-C5 alkoxy, C1-C5 alkylsulfonyl, di(C1-C5 alkyl)amino, nitrogen-containing heterocyclic, aryl, and C1-C5 heteroaryl; R4 is selected from any of substituted or unsubstituted aryl C1-C5 alkyl and nitrogen-containing saturated heterocyclic C1-C5 alkyl. This compound can be used as a TDP1 inhibitor for antitumor therapy.

The present invention provides a long-acting dual-target chimeric antigen receptor, nucleic acid molecule, recombinant vector, cell, and application thereof. The dual-target chimeric antigen receptor comprises two independent transmembrane protein chains, wherein the first CAR chain targets a scFv of the first target, and the intracellular signal comprises a second signal and an intracellular transduction signal or only an intracellular transduction signal; the second CAR chain targets a scFv of the second target, and the intracellular signal comprises a costimulatory signal and a JAK enzyme activation transduction domain. The CAR-T cells prepared by the present invention have a strong and persistent killing effect on tumor cells that simultaneously express the first and second targets, and can be used for the anti-tumor treatment of solid tumors.

This invention belongs to the pharmaceutical field, specifically relating to an anti-tumor angiogenesis drug potentiator, an anti-tumor drug composition, and its application. Firstly, this invention discovers that SHCBP1 inhibitors can enhance the therapeutic effect of anti-tumor angiogenesis drugs and can be used as potentiators for anti-tumor angiogenesis drugs. Secondly, when SHCBP1 inhibitors are used in combination with anti-tumor angiogenesis drugs, or in combination with anti-tumor angiogenesis drugs and PD-1 inhibitors, tumor angiogenesis can be normalized and its window period prolonged, significantly improving the efficacy of immunotherapy, anti-angiogenesis, and anti-tumor therapy, showing broad application prospects.

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.

This invention provides a chlorambucil NO donor prodrug having the structure shown in Formula (I) or a pharmaceutically acceptable salt thereof: Formula (I). It involves reacting chlorambucil with a dihaloalkane to obtain a halochlorambucil intermediate; reacting the halochlorambucil intermediate with silver nitrate to obtain the chlorambucil NO donor prodrug. This invention applies the chlorambucil NO donor prodrug to the preparation of drugs for treating tumors, such as melanoma, lymphoma, leukemia, or breast cancer. This nanosystem exhibits good NO release levels under light irradiation. Cellular experiments have demonstrated its good antitumor effect, providing a new strategy for multimodal combined antitumor therapy.

The invention provides maslinic acid PROTACs as well as a preparation method and application thereof, and belongs to the technical field of drug development. According to the invention, maslinic acid is taken as a POI ligand, lenalidomide and fluoro-thalidomide are taken as E3 ligands, and linker selects a PEG chain or an aliphatic chain, so that the anti-cancer activity of the compound is superior to that of maslinic acid, and the compound has a good potential application prospect in the aspect of anti-tumor treatment.

The invention belongs to the technical field of biological medicine, and discloses a medicine for in-vivo engineering CAR-T and a preparation method thereof. The drug provided by the invention comprises a first RNA and a second RNA which are used for coding a chimeric antigen receptor in a specific molar ratio, the second RNA is used for coding at least two cytokines of CCL19, IL-17, IL-15, IL-2 or IL-24, by adopting the drug, the gene delivery efficiency and targeting of in-vivo engineered CAR-T can be improved, better T cell transformation and CAR + T cell generation effects are realized, the CAR-T cell depletion is reduced, and the drug has a good application prospect. According to the present invention, the CAR-T gene is constructed, such that the CAR-T gene can survive for a long time in the tumor microenvironment and continuously provide the treatment effect, has the excellent anti-tumor treatment effect, has the excellent application prospect in the in-vivo engineering CAR-T treatment, and has the important significance on the promotion of the efficient, safe and economical development of the CAR-T treatment.

The present invention relates to the field of biomedicine, and in particular to immunogenic cell death-enhancing nanovesicle hydrogels and their applications. The present invention provides a 3D-printable, multifunctional, synergistic immunogenic cell death-enhancing nanovesicle hydrogel. The hydrogel uses SerMA hydrogel as a matrix and encapsulates cell membrane nanovesicles (N@ILO) loaded with the photothermal agent IR1061, the chemotherapy drug OXA, and the tumor acidic microenvironment regulator Lon. The hydrogel triggers initial tumor immunogenic cell death through the photothermal effect, further enhances the ICD effect through OXA, and modulates the acidic tumor microenvironment through Lon to increase T cell activity, achieving multimodal synergistic anti-tumor therapy after surgery. The hydrogel also possesses excellent photocurable 3D printing capabilities and can be used to construct personalized filling structures that match postoperative defect areas. The hydrogel has broad application prospects and provides a new strategy and theoretical basis for the comprehensive postoperative treatment of choroidal melanoma.

Tumor-selective expression of therapeutic molecules by bacteria is achieved by one or more AND, NOR, OR, NOT and / or NAND gate genetic circuits. The therapeutic molecules can be proteins, metabolites or catabolites, and may also be immunotherapeutics or immunotherapeutic cytotoxins. Single or multiple expression components may be used. Tumor selective expression of multimeric proteins utilizes multimerization as to complete the genetic circuit. Genetic circuits that are unlinked, function to achieve a combined effect on specificity of delivery of antitumor therapeutic molecules. Compositions and methods to generate silica, PEG and Poly-HPMA coated bacteria are also provided. Compositions and methods for selectively sensing or imaging tumors are also described.

The invention provides a pAKT-targeted small molecule compound, a PET molecular probe precursor, a PET molecular probe and a preparation method and application of the PET molecular probe. The PET molecular probe disclosed by the invention is a radioactive probe which is modified on the basis of a chemical structure of a medicine Caprivastib (AZD5363) and is marked by 68Ga and is targeted to pAKT. According to the probe, structural modification is carried out on Capivasertib, the area, combined with PKA, of Capivasertib is changed, precursor molecules combined with pAKT in a high-specificity mode are obtained, and the precursor molecules are further researched, developed and modified into the radioactive probe targeting pAKT capable of being used for PET imaging. The probe has relatively low abdominal nonspecific uptake, can effectively distinguish tumors with high expression and low expression of pAKT in vivo, and can predict and early evaluate the response condition of the tumors to a PI3K / AKT pathway related inhibitor. Therefore, the probe has a very strong clinical application prospect, on one hand, the probe can be used for analyzing the expression quantity of pAKT in tumor tissues; on the other hand, the probe can also be used for predicting and early evaluating the effect of the PI3K / AKT pathway related inhibitor in anti-tumor treatment.

The present invention relates to an EZH1 / 2 inhibitor, a preparation thereof, and a use thereof in anti-tumor therapy, specifically comprising a compound represented by formula I or formula II, or a deuterated compound, or a stereoisomer, or a pharmaceutically acceptable salt thereof, and further comprising a pharmaceutical composition of the compound, and a use of the foregoing as an EZH1 / 2 inhibitor in the preparation of medication for treating related diseases.

This invention provides a chimeric antigen receptor comprising an NFIX-encoding gene, a self-cleaving peptide sequence F2A, and a CAR-encoding sequence. The NFIX-encoding gene is located upstream and is linked to the CAR-encoding sequence via the self-cleaving peptide sequence F2A. The sequence of the NFIX-encoding gene is shown in SEQ ID NO. 01, and the sequence of the self-cleaving peptide sequence F2A is shown in SEQ ID NO. 03. This invention also provides a chimeric antigen receptor T cell expressing the aforementioned chimeric antigen receptor. This invention further provides the application of the aforementioned chimeric antigen receptor or the aforementioned chimeric antigen receptor T cell in the preparation of drugs for treating cancer. This invention improves the antitumor therapeutic effect of CAR-T cells by introducing the NFIX expression element into engineered T cells, thereby enhancing their functional stability, proliferative capacity, and cytotoxic activity under continuous antigen stimulation.

The application discloses a 2,2'-biquinoline-4,4'-dicarboxylic aliphatic amino acid derivative, and a preparation and application thereof, and belongs to the technical field of medicines.The structure of the 2,2'-biquinoline-4,4'-dicarboxylic aliphatic amino acid derivative is shown in the following formula: wherein RNH is selected from the group consisting of structures that are stable, have low toxicity, have antitumor activity, and can be used as effective components of antitumor drugs for antitumor treatment.The preparation process of the 2,2'-biquinoline-4,4'-dicarboxylic aliphatic amino acid derivative is simple, and the 2,2'-biquinoline-4,4'-dicarboxylic aliphatic amino acid derivative is easy to be industrialized when being used for preparing antitumor drugs.

The invention belongs to the cross technical field of cell engineering, nano-drugs and biological manufacturing, and particularly discloses a drug-loaded vesicle based on denucleated cells as well as a preparation method and application of the drug-loaded vesicle. According to the invention, a cell suspension and a cytoskeleton relaxant are co-incubated to relax an actin skeleton and weaken nucleoplasm connection; then loading the treated cell suspension on a multi-layer discontinuous density gradient centrifugal medium, realizing physical separation of cell nucleuses and cytoplasm through high-speed centrifugation according to buoyancy density difference, and collecting components of a specific interface to obtain high-purity denucleated cells with a complete membrane structure; then co-incubating the denucleated cells and ROS response type lipidosome (co-carrying therapeutic siRNA and a sound-sensitive agent Ce6) prepared in advance, so that the lipidosome is wrapped or anchored by a denucleated cell membrane; finally, the composite system is subjected to extrusion treatment through a microporous membrane, the drug-loaded vesicles uniform in particle size and stable in structure are obtained, and the drug-loaded vesicles are suitable for various application scenes such as anti-tumor treatment and RNA vaccine delivery.

The invention provides a paclitaxel precursor nano-drug as well as a preparation method and application thereof, and belongs to the technical field of medicinal chemistry. Comprising a paclitaxel dimer prodrug and 7-ethyl10-hydroxy-camptothecin loaded on the paclitaxel dimer prodrug. According to the invention, a paclitaxel dimer prodrug is used as a self-assembly monomer to construct a PTX-SN38 synergistic treatment nano system, and the system has the advantages of dispersibility in water, biocompatibility, tumor specific response, synergistic treatment and the like, and can effectively solve the limitation of paclitaxel and SN38 in anti-tumor treatment.

This invention discloses a class of non-conjugated N-methyl site-linked photosensitive dyes, their preparation methods, and applications, relating to the field of fine chemical organic dye technology. The photosensitive dyes have the structure of general formula 1. These non-conjugated N-methyl site-linked photosensitive dyes possess no heavy atom modification, dual-cation characteristics, and exhibit near-infrared absorption and emission, high molar extinction coefficient, and high photosensitization efficiency, specifically generating type I and type II reactive oxygen species. They demonstrate excellent tumor cell killing ability under near-infrared light irradiation, showing promising application prospects in anti-tumor therapy.

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 belongs to the field of medicinal chemistry and pharmacology, and relates to application of a novel glycolipid TLR2 agonist 13-C in preparation of vaccine adjuvants and anti-tumor treatment. The compound is excellent in human TLR2 agonist activity, EC50 reaches 2.2 nM, and the compound is simple in structure, easy to prepare and excellent in solubility and has industrial application potential. In a B16-OVA tumor model, the antibody induction capacity of the compound is superior to that of a positive control drug Diprovocim, and the anti-tumor activity of the compound is more remarkable; in addition, PD-L1 expression of tumor tissue can be effectively down-regulated, and a synergistic anti-tumor effect is generated with a PD-L1 monoclonal antibody Atezolizumab. Besides, 13-C and a vaccine adjuvant QS-21 are combined for use, so that a synergistic enhancement effect is achieved, the antibody titer induced by a vaccine can be remarkably improved, antibody subtypes are enriched, meanwhile, cellular immunity and humoral immunity response of an organism are stimulated, and the effect of dual immune activation is achieved.

The present invention belongs to the technical field of pharmaceutical carriers for targeting tumors, and specifically relates to a targeted tumor carrier based on lactic acid bacteria vesicles, and its preparation method and application. The targeted tumor carrier based on lactic acid bacteria vesicles of the present invention comprises lactic acid bacteria vesicles and DSPE-PEG2000-cRGD anchored on the surface of the lactic acid bacteria vesicles. The targeted tumor carrier of the present invention can effectively and actively deliver SR-18292 and doxorubicin into tumor cells, thereby effectively inhibiting tumor cell apoptosis, significantly inhibiting tumor cell migration and invasion, and thus exerting a significant anti-tumor therapeutic effect. In addition, the tumor drug delivery system of the present invention has good biosafety.

The invention provides a combined ablating agent based on spontaneous heating and a preparation method and application thereof, and belongs to the technical field of medical materials. The LipoCA provided by the invention comprises a lipidosome, and CaO and silver nanoparticles which are wrapped in the lipidosome. In the invention, the lipidosome is used as a permeation barrier, CaO is wrapped in the lipidosome, the contact of CaO with H2O molecules and H < + > in a tumor microenvironment is delayed through a physical isolation effect, so that the exothermic reaction is accurately regulated and controlled, the Ag NPs can destroy a calcium metabolism steady state, induce Ca < 2 + > enrichment in tumors, mediate ROS production and promote cell apoptosis, and the Ag NPs, the CaO and the lipidosome have a synergistic effect, so that an exothermic effect is achieved. The composite material can improve the minimally invasive precise treatment of cancers, effectively avoids thermal burns of adjacent blood vessels and nerves, and has multiple functions of regulating and controlling the exothermic reaction rate, inhibiting thermal diffusion, inducing ROS (reactive oxygen species) generation and occluding blood vessels in tumors so as to enhance the thermal ablation curative effect and anti-tumor treatment.

This invention belongs to the field of nanocarrier and immunotherapy technology, specifically relating to a lipid nanoparticle targeting tumor-associated macrophages, a combined delivery method, and its application in tumor immunotherapy. The lipid nanoparticles targeting CD206 tumor-associated macrophages constructed in this invention are used for efficient in vivo delivery of multifunctional nucleic acid molecules, achieving immune regulation, gene editing, and anti-tumor therapy. This invention achieves targeted delivery and multifunctional synergistic effects through lipid particle design, nucleic acid sequence design, and in vitro and in vivo functional verification. Through in vivo delivery of ipLNPs, macrophages can simultaneously achieve: 1) expression of anti-PD-L1 antibodies, blocking immunosuppressive signals; 2) expression of HER2-CAR structures, enhancing phagocytosis and killing ability against tumors; and 3) remodeling of the tumor immune microenvironment through CRISPR / Cas9-mediated FN1 knockout. The lipid nanoparticles constructed using this invention can solve the problem of insufficient targeting of immune cells in the tumor microenvironment by traditional LNP delivery systems.

The application discloses a kind of synergistic antitumor porphyrin-based covalent organic framework heterojunction materials and preparation method thereof, belong to biological medicine technical field. 5,10,15,20-tetra (4-aminobenzene) -21H,23H-porphyrin and 2,5-divinyl benzene formaldehyde are added to organic solvent to carry out solvothermal reaction, and porphyrin-based covalent organic framework (pCOF) is obtained;pCOF is mixed with 1,2-ethanedithiol and heated to obtain thiolated modified pCOF;Thiolated modified pCOF is stirred with glutathione aqueous solution ultrasonically, then tetra-chloroauric acid is added to carry out reaction, and synergistic antitumor porphyrin-based covalent organic framework confined gold nanocluster heterojunction material, recorded as Au@pCOF, is obtained.The Au@pCOF prepared in the application can be used as a kind of biocompatible antitumor therapeutic agent, under the irradiation of 808 nm near-infrared light, active oxygen is efficiently generated and heat is released, photothermal and photodynamic synergistic enhancement is realized, tumor cells are significantly killed, and is used for space-time integration synergistic antitumor therapy.

This invention discloses a STAT3-mutated cell product and its uses, belonging to the interdisciplinary field of genetic engineering and tumor immunotherapy. Through saturation mutation screening, this invention is the first to discover that STAT3 gain-of-function mutations promote CAR-T anti-tumor responses. Furthermore, through cell and animal experiments, it is demonstrated that activating STAT3 can alleviate CAR-T cell immune exhaustion and significantly enhance the in vivo and in vitro killing ability of CAR-T cells against tumor cells, thereby improving the efficacy of anti-tumor therapy. This invention provides a new therapeutic target and strategy for the field of tumor immunotherapy, possessing significant scientific and clinical application value.

The invention belongs to the technical field of preparation of microorganisms and medicines, and particularly relates to a compound FK228D as well as a preparation method and application thereof. The compound provided by the invention is obtained by carrying out culture and liquid fermentation on a Burkholderia thailantensis E264 [delta] tdp:: R-tdp-dep-M4spi which is a mutant strain of Burkholderia thailantensis, and separating the Burkholderia thailantensis from a fermentation liquid of the Burkholderia thailantensis E264 [delta] tdp:: R-tdp-dep-M4spi. In addition, the invention also discloses an application of the FK228 derivative or the pharmaceutically acceptable salt thereof in preparation of antitumor drugs. Experiments prove that the compound 1 produced by the burkholderia mutant strain can obviously inhibit the growth of tumor cells and has no influence on the growth of normal cells. Therefore, the compound provided by the invention is expected to gain the application value in anti-tumor treatment, a new alternative compound is provided for development and application of novel anti-tumor drugs, and the compound has remarkable economic value and social benefit.