43results about How to "Increase lethality" patented technology

This invention discloses a portable low-temperature plasma device based on a Laval nozzle structure and its application, belonging to the field of plasma technology application technology. Specifically, it includes (1) the construction of the device; and (2) the use of the device for fungal eradication treatment and transdermal drug delivery enhancement treatment. The beneficial effects achieved by this invention are as follows: This invention is the first to apply the Laval nozzle structure to a portable low-temperature plasma device. The results show that the device can effectively improve the plasma jet performance and active particle content, significantly improve the treatment effect of fungal infections of the skin and nails and the transdermal drug penetration efficiency, while solving the problems of large size, reliance on external power supply, and complex operation of traditional plasma devices. Therefore, using this invention for the treatment of fungal infections of the skin and nails and for enhanced transdermal drug delivery has advantages such as ease of operation, high safety, non-invasiveness, and high efficiency, and thus has potential application prospects in the field of skin disease treatment and transdermal drug delivery.

This application relates to the technical field of immunotherapy, specifically disclosing a CAR targeting human HER2, the CAR gene and its recombinant vector, CAR-M cells, their preparation methods, and applications. This application discloses a CAR targeting human HER2, comprising a leader peptide, an extracellular recognition region, a hinge region, a transmembrane region, and an intracellular signaling domain; the extracellular recognition region is a single-chain antibody binding to tumor antigens; the transmembrane region is any one of FcγRⅠ, FcγRⅡ, FcγRⅢ, FCER1G, and CD36 capable of activating macrophage phagocytic signals; the intracellular signaling domain is the P2 domain with the amino acid sequence shown in SEQ ID NO.5. This application also discloses a CAR gene targeting human HER2 and its recombinant vector. CAR-M cells prepared using the above-mentioned CAR targeting human HER2 exhibit strong phagocytic and killing abilities against target cells.

This invention relates to the fields of brachytherapy and radiosensitization, specifically providing a... 125 I-nano implantable particles, their preparation methods, and applications. 125 The 1-nanometer implanted particles have a core-shell structure, consisting of a particle core and particles adsorbed on the outer surface of the particle core. 125 I and the particles encapsulated in the nucleus and 125 The outer shell of the I-type photosensitizer is a covalent organic framework. This invention... 125 The core of the I-nanometer implanted particle is used to enhance the energy deposition of gamma rays and X-rays, generating more hydroxyl radicals; the shell containing a type I photosensitizer is used to absorb the energy of Auger electrons and internal conversion electrons and excite the photosensitizer to generate singlet oxygen, effectively improving the response to... 125 The efficiency of I decay energy utilization. 125 I-nano implanted particles, combined with internal radiation therapy and radiodynamic therapy, destroy tumor cell DNA and cell membranes, enhance tumor killing and induce immunogenic cell death, thereby activating anti-tumor immunity and inducing remote effects.

The present application belongs to the field of disease treatment and immunology, in particular, the present application discloses an antibody or antigen-binding fragment thereof against CD73, a nucleic acid molecule encoding the same, an immunoconjugate, a bispecific molecule and a pharmaceutical composition comprising the same, and the use thereof for enhancing an immune response and / or treating a tumor.

The invention discloses an application of targeted improvement of a high-potassium microenvironment in osteosarcoma immunotherapy, vanadium disulfide nano-particles are synthesized by taking vanadyl acetylacetonate as a raw material and adopting a high-temperature oil phase method, the particles can be accelerated to decompose at 42 DEG C or above so as to release hydrogen sulfide and vanadate, the vanadate can be specifically combined with E2 conformation of Na < + >-K < + >-ATP enzyme, and thus the stability of the particles is improved. According to the present invention, the HSP protein is released, the conversion of the HSP protein to E1 conformation is blocked, the continuous inward flow of K < + > is inhibited, such that the potassium ion concentration in the T cell is reduced, the function inhibition on the T cell is relieved, and the released hydrogen sulfide can further enhance the thermal effect by inhibiting the HSP protein so as to form the ion regulation-immune activation dual mechanism to improve the T cell killing ability. According to the scheme, the high potassium ion level of the osteosarcoma microenvironment is regulated and controlled through vanadate, hydrogen sulfide can enhance immune response and improve the anti-tumor function of T cells by enhancing the heat effect and the synergistic effect of vanadate, and an efficient and low-toxicity new strategy is provided for osteosarcoma treatment.

The application discloses application of a small-molecule compound targeting TIM-3 in tumor immunotherapy and relates to the technical field of immunology and antitumor drugs. The small-molecule compounds DTS and CT are safe and verified marketed drugs, and it is found that the small-molecule compounds can bind to TIM-3 protein and regulate T cell exhaustion related to TIM-3. + Experiments prove that DTS and CT can effectively inhibit CD8 T cell exhaustion, promote expansion of exhausted precursor T cells, and comprehensively enhance T cell antitumor immune function. In a melanoma model, the compounds significantly inhibit tumor growth and reduce the proportion of tumor-infiltrating T cell exhaustion. The application uses the strategy of "new use of old drugs", provides a TIM-3 small-molecule inhibitor with high safety, oral administration, strong penetration and low cost, effectively solves the clinical transformation predicament of existing antibody drugs and newly synthesized small molecules, and provides a new scheme for rapid transformation of tumor immunotherapy.

The invention discloses a bispecific antibody targeting CD3 and PD-L1 and an application of the bispecific antibody. The bispecific antibody comprises a first antigen binding region, a second antigen binding region and an Fc part, the Fc part comprises a first Fc peptide fragment and a second Fc peptide fragment; the first antigen binding region comprises an scFv fragment and a binding protein of a first molecule or a fragment thereof, the binding protein of the first molecule or the fragment thereof is connected with the N end of the scFv fragment, and the C end of the scFv fragment is connected with the N end of the first Fc peptide fragment; the second antigen binding region comprises a binding protein of a second molecule or a fragment thereof, and the binding protein of the second molecule or the fragment thereof is connected with the N end of the second Fc peptide fragment; the first molecule and the second molecule are PD-L1, and the scFv fragment has CD3 binding activity. The bispecific antibody disclosed by the invention is good in safety, high in anti-cancer activity and high in clinical application and drug development value.

The application belongs to the technical field of cell engineering, and particularly relates to a bispecific antibody targeting CD22 and CD19, a chimeric antigen receptor thereof and application. In the bispecific antibody, a CD22 light chain and a CD22 heavy chain are connected through a linker 4 to form a CD22 single-chain antibody, and a CD19 light chain and a CD19 heavy chain are connected through a linker 4 to form a CD19 single-chain antibody, which comprises one of the following structures: (1) the CD22 single-chain antibody and the CD19 single-chain antibody are connected through a linker 1 or a liner 2; (2) the two ends of the CD19 single-chain antibody are connected with the CD22 light chain and the CD22 heavy chain through a linker 3, respectively. The chimeric antigen receptor provided by the application can simultaneously target two different tumor antigens, improve the killing of tumor cells, reduce the probability of immune escape, and reduce the tumor recurrence rate after CAR-T treatment.

This invention belongs to the field of biotechnology, specifically relating to a high-affinity anti-tumor NK cell, its preparation method, and its application. This invention designs NK92 cells transfected with a haPD1 high-affinity chimeric conversion receptor, wherein the high-affinity chimeric conversion receptor includes the extracellular segment of haPD-1, the transmembrane segment of CD28, the intracellular segment of DAP10, and the intracellular segment of CD3ζ. This invention prepares haChR3-NK92 cells through the construction of a recombinant lentiviral vector, lentiviral packaging, and lentiviral transfection of NK92 cells. In this invention, haPD-1 serves as the extracellular recognition domain of the CAR structure, specifically binding to PD-L1 on tumor cells to achieve a stronger tumor-killing effect. The co-stimulatory molecule CD28 serves as the transmembrane region to transmit extracellular information into the cell, integrating the adaptor protein DAP10 of the NK cell surface activator receptor NKG2D into the cell, and further embedding the intracellular segment CD3ζ commonly used in CAR design to jointly promote NK cell activation. The preparation method of this invention can successfully construct haChR3-NK92 cells, achieve the expression of the target plasmid, and be applied in anti-tumor drug research.

The invention relates to an application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer, and particularly relates to the following aspects: (1) osimertinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), and shows a remarkable curative effect in treatment of non-small cell lung cancer (NSCLC) patients carrying specific EGFR mutation; (2) chidamide is a novel oral HDACi, can induce cell apoptosis, cell cycle arrest and cell growth inhibition, and shows good tolerance and antitumor activity in various cancer types; and (3) chidamide is taken as an epigenetic regulating agent and can be in synergistic effect with osimertinib, so that the capability of killing lung cancer cells is enhanced. The invention belongs to the technical field of medicines, and particularly provides application of osimertinib combined with chidamide in treatment of osimertinib drug-resistant lung cancer.

Provided is a drug useful for photoimmunotherapy. Specifically, provided is a conjugate including an antibody molecule, a particle having an average particle diameter of 100 nm or less, and a photosensitive portion. In the conjugate, the particle having an average particle diameter of 100 nm or less is linked to the antibody molecule, and at least one of the antibody molecule or the particle is bound to the photosensitive portion. The photosensitive portion is a portion showing increase of hydrophobicity when irradiated with a light beam having a wavelength of from 500 nm to 900 nm or a portion containing a phthalocyanine skeleton.

This invention belongs to the field of novel carbon nanomaterials technology, and discloses a Clostridium butyricum-derived carbon dot boat-shaped nanoparticle, its preparation method, and its application. The preparation method includes the following steps: Step 1, Clostridium butyricum is cultured to the logarithmic growth phase, and then placed in a pretreatment solution for suspension incubation to regulate the structural integrity and surface chemical composition of Clostridium butyricum cells. The pretreatment solution is an aqueous solution of EDTA, NaCl, or PEG-8000. After incubation, the precipitate is collected by centrifugation, washed, and resuspended in ultrapure water; Step 2, the Clostridium butyricum treated in Step 1 is placed in a high-pressure reactor for hydrothermal reaction to obtain a crude product system; Step 3, the crude product system is filtered and purified, and freeze-dried to obtain Clostridium butyricum-derived carbon dot boat-shaped nanoparticles. The nanoparticles prepared by this invention have uniform particle size, good water solubility, dispersibility, and biocompatibility, and exhibit significant immunomodulatory functions.

This invention provides a method for mutagenesis of *Aspergillus cristatus* and its application, belonging to the field of microbial technology. The mutagenesis method provided by this invention includes the following steps: first, pretreating *Aspergillus cristatus* suspension by mixing it with a compound enzyme solution; then culturing the pretreated *Aspergillus cristatus* in a culture medium supplemented with a mutagen; the compound enzyme solution consists of a cell-lysing enzyme solution and a β-glucanase solution; the mutagen includes ethyl methanesulfonate and / or diethyl sulfate. This invention can improve the efficiency of the mutagen entering the bacterial cells, thereby enhancing the mutagenesis effect; the mutant strains obtained by mutagenesis, compared to the original strain, exhibit more vigorous colony growth on plates, larger average diameter, denser hyphae, and / or better morphological stability. Furthermore, it can achieve ideal mutagenic selection pressure at lower mutagen concentrations and shorter treatment times, reducing sublethal damage, which is beneficial for the recovery and screening of mutant strains and improving the efficiency of mutagenesis experiments.

The invention discloses application of USP15 in preparation of a bladder cancer radiotherapy sensitizer, and belongs to the technical field of biological medicine. The objective of the invention is to improve the radiotherapy sensitivity of bladder cancer. The invention relates to an application of USP15 in preparation of a bladder cancer radiotherapy sensitizer. The USP15 is used for preparing the bladder cancer radiotherapy sensitizer. The radiotherapy sensitivity of the bladder cancer is improved by overexpressing the USP15. The USP15 can regulate and control the stability of FIS1 protein through ubiquitination modification so as to inhibit the mitochondrial function, and the activation of the regulation and control pathway is the core mechanism of the USP15 for exerting the radiotherapy sensitization effect. In conclusion, the invention not only provides a new thought for molecular mechanism research of bladder cancer radiotherapy sensitization, but also provides a potential strategy for treatment of clinical radiotherapy resistant bladder cancer patients, and has important drug development value and clinical application prospect.

This invention belongs to the field of biomedical technology and discloses a chimeric antigen receptor targeting CD20, its gene expression construct, and its applications. The chimeric antigen receptor provided by this invention specifically includes an amino acid fragment with the sequence shown in SEQ ID NO:29 or a variant fragment having at least 85% sequence identity with SEQ ID NO:29. Its functional fragments, including the signal peptide, antigen-binding region, hinge region, transmembrane region, intracellular co-stimulatory domain, and signal transduction domain, form an organic whole, working synergistically to endow the chimeric antigen receptor with good CD20-targeting binding, T-cell activation, and cell-killing effects, demonstrating excellent application potential in the preparation of drugs for the treatment of relapsed / refractory B-cell malignancies.

This invention relates to mini-binding proteins targeting TROP2, their drug conjugates, and their applications. The mini-binding proteins comprise amino acid sequences selected from any of SEQ ID Nos. 7-12. The invention further provides conjugates of the aforementioned mini-binding proteins with small molecule toxin drugs. Experiments have demonstrated that the conjugates of the mini-binding proteins and small molecule toxin drugs of this application can target and kill TROP2-positive tumor cells, showing promise as drugs for the treatment of TROP2-positive tumors.

This invention provides an antibody-drug conjugate in which a compound of Formula 1 or a pharmaceutically acceptable salt, stereoisomer, tautomer, prodrug, hydrate, solvate, or isotopically labeled analogue thereof is linked to an anti-Nectin-4 antibody via a linker. The antibody-drug conjugate according to this invention can selectively exhibit the activity of the compound of Formula 1 on cancer cells expressing Nectin-4.

The application provides a microneedle preparation for jointly delivering photothermal nanolaser and elemene and a preparation method and application thereof. The application first prepares a novel photothermal nanolaser Au@MoS2 through a two-step aqueous phase synthesis strategy. Benefiting from the synergistic effect of the hybrid material, the nanolaser exhibits significantly enhanced near-infrared (NIR) photothermal effect, peroxidase (POD) activity and glutathione peroxidase (GSHOx) activity, can effectively remodel the tumor microenvironment and destroy the oxidation-reduction homeostasis. Further, the application successfully prepares a novel soluble microneedle preparation through a template method by taking the photothermal nanolaser, beta-ELE and hyaluronic acid as raw materials. The novel composite microneedle of the application is in a sharp quadrangular pyramid shape, and can effectively inhibit the growth of melanoma through transdermal delivery of the photothermal nanolaser and beta-ELE and has no significant systemic toxicity, thereby providing an innovative strategy for non-invasive, efficient and safe combined treatment of melanoma.

The invention provides a dual immune checkpoint co-blocking agent for targeting EGFR (epidermal growth factor receptor), the blocking agent is prepared into a target polypeptide molecule by an Fmoc solid phase polypeptide synthesis method, and the polypeptide molecule has a self-assembly behavior in a solution containing EGFR protein; the critical assembly concentration of polypeptide molecules triggered by EGFR protein is 18.2 [mu] M, and nanofibers with the diameter of 8.5 nm are formed through the self-assembly behavior; the nanofiber captures membrane cholesterol and induces membrane vesicles to fall off through a high-density hydrophobic area of the nanofiber, so that EGFR and cholesterol are removed at the same time, and the following dual effects are achieved: 1, biochemical immune checkpoint blocking: reduction of EGFR causes reduction of STAT3 phosphorylation level, and further down-regulation of PD-L1 expression; 2, biomechanical immune checkpoints are blocked, wherein cholesterol is removed, so that the rigidity of tumor cell membranes is remarkably improved, and the sensitivity of the tumor cell membranes to mechanical attack of T cells is enhanced; the blocking agent can significantly improve the killing effect of T cell immunotherapy such as CAR-T cells on solid tumors.

This invention belongs to the field of nanomaterials technology, and more specifically, relates to indocyanine green-stabilized CuET nanoparticles, a nanoparticle dispersion, a preparation method thereof, and its applications. The indocyanine green-stabilized CuET nanoparticles provided by this invention are nanoparticles formed by stabilizing CuET nanocrystals with indocyanine green, wherein indocyanine green binds to and stabilizes the CuET nanocrystals through hydrophobic interactions, forming the indocyanine green-stabilized CuET nanoparticles. The indocyanine green-stabilized CuET nanoparticles provided by this invention can improve the water solubility and serum stability of CuET, facilitating intravenous administration of CuET. Furthermore, the indocyanine green-stabilized CuET nanoparticles provided by this invention can disrupt mitochondrial function of tumor cells, inhibit tumor cell respiration, improve hypoxia at the tumor site, and enhance the photodynamic antitumor therapeutic effect mediated by indocyanine green.

This invention discloses a class of tumor-targeting prodrug compounds that synergistically enhance photodynamic / chemotherapy through azoreductase activation, their preparation method, and their application in selectively killing cancer cells and treating tumors. The first objective is to provide a class of tumor-targeting prodrug compounds that synergistically enhance photodynamic / chemotherapy through azoreductase activation. These compounds possess the properties of positively charged cyanine dyes, allowing them to target tumor sites and localize to the mitochondria of cancer cells to a certain extent. Through simultaneous activation of azoreductase, photosensitizers and chemotherapeutic drugs are released, achieving selective killing of cancer cells and targeted tumor therapy. The second objective is to provide a method for preparing the prodrug compound. In an anhydrous system, an indole compound containing an R1 group and modified with different substituents at the benzene ring position is reacted with 2-chloro-3-(hydroxymethylene)-1-cyclohexene-1-carboxaldehyde to obtain compound IV. Then, compound IV is reacted with m-nitrophenol and reduced to obtain compound V. Finally, compound V undergoes a diazotization reaction with sodium nitrite, and a compound containing an R2 group is added to continue the reaction to obtain the target prodrug compound.

The invention provides a copper-hyaluronic acid composite nanomaterial as well as a preparation method and application thereof. Metal copper ions (Cu < 2 + >) and bovine serum albumin form a precursor solution, then the precursor solution and sodium carbonate are co-precipitated to form a basic cupric carbonate precursor, hyaluronic acid is added, the hyaluronic acid is covalently modified on the surface of the nano material through an amido bond, and finally dialysis purification is performed to remove unreacted hyaluronic acid and other byproducts. The method has the characteristics of simple production process, low raw material cost, high yield, good reproducibility and the like, and low-cost large-scale production can be realized under normal conditions at room temperature. The preparation method has remarkable advantages in preparation of solid tumor treatment drugs, and combines the antitumor activity and immune activation of copper ions and the targeting delivery characteristic of hyaluronic acid to form a multi-mechanism synergistic treatment strategy.

The application discloses an oxygen-enhanced pH-responsive magnetic targeting photosensitizer delivery system, which is recorded as Fe3O4@mSiO2@MnO2@PS@PEG-b-PAsp, and the delivery system takes the superparamagnetic Fe3O4 core as a magnetic targeting matrix, is covered with mesoporous silica outside, and is crosslinked with polyethylene glycol-polyaspartic acid after being modified by amino on the surface of the mesoporous silica, so that the loading of the photosensitizer is realized. The oxygen-enhanced pH-responsive magnetic targeting photosensitizer delivery system provided by the application realizes the magnetic targeting property and the pH responsiveness, and realizes the effect of increasing the concentration of intracellular reactive oxygen species.

The invention provides a polyvinylpyrrolidone modified cerium-based UIO-66 nano material as well as a preparation method and application thereof, and relates to the technical field of nano materials, catalysts and antitumor drugs. According to the method, cerium ions are used as metal nodes, terephthalic acid is used as an organic connector, a crystal framework with a UIO-66 characteristic topological structure is formed, then, polyvinylpyrrolidone is introduced into framework nano particles in situ through solvothermal reaction, and the nano particles are prepared. Therefore, the polyvinylpyrrolidone modified cerium-based UIO-66 nano material which is uniform in morphology and good in dispersity and has an efficient piezoelectric effect and peroxidase activity is obtained. The cerium-based UIO-66 nano-material disclosed by the invention can obviously enhance the catalytic performance under remote and accurate regulation and control of ultrasonic waves, and excites an additional biological catalytic function, so that the defect of single treatment is overcome through multi-mechanism synergy, and high-efficiency, low-toxicity and controllable treatment on tumors is realized.

The present invention provides an engineered immune cell targeting BCMA and use thereof. In particular, the present invention provides a CAR specifically targeting BCMA, the CAR comprising an antigen-binding domain which is an S-derived scFv, an antibody heavy chain variable region as shown in SEQ ID NO: 9 and an antibody light chain variable region as shown in SEQ ID NO: 10. The present invention also provides a CAR-T cell comprising the CAR, a double CAR- and CAR-T cell comprising the S-derived scFv, and related use thereof. Compared to CAR-T cells constructed using other scFvs, the constructed CAR-T cell of the present invention has a better killing effect and tumor elimination capability.

The invention discloses an application of cholesterol synthetase in preparation of a product for enhancing the killing function of CAR-T cells and derivatives thereof, the cholesterol synthetase is SQLE or LSS, and the product enhances the killing function by separately knocking out the SQLE or separately overexpressing the LSS in the CAR-T cells and the derivatives thereof. According to the application, a cholesterol synthesis key enzyme SQLE is knocked out or LSS is overexpressed, so that the killing ability of CAR-T cells and derivatives thereof is remarkably enhanced.

The present application provides a bactericide for fracturing, comprising a solvent, a bactericidal liquid and a bactericidal microcapsule; a main material of a wall material of the microcapsule comprises urea-formaldehyde resin and chitosan in a mass ratio of (8-10):1; a main material of a core material of the microcapsule comprises chlorine dioxide, isothiazolinone, dodecyl dimethyl benzyl ammonium chloride and sophoramine in a mass ratio of (5-8):5:2:1; and a mass ratio of the main material of the core material to the main material of the wall material is 1:(1-2). Meanwhile, the present application also provides a preparation method of the bactericide, which is simple, easy to operate and suitable for industrial application.

The present application provides an antibody or antibody fragment. It comprises heavy chain complementarity determining regions HCDR1, HCDR2 and HCDR3, and light chain complementarity determining regions LCDR1, LCDR2 and LCDR3; HCDR1 is selected from GYTFSSFS, GYTFSTFA or GYSFTAYT, HCDR2 is selected from ILPGSNST, ILPGINNT, ILPGGNNT or INPYNGGT, and HCDR3 is selected from SSYWFAY, STYWFAY or AREGNYYGSRGDFDY; LCDR1 is selected from QSLLNSGNQKNY or QTIVTN, LCDR2 is selected from GAS or YAS; and LCDR3 is selected from QNAHSYPPT, QNAHSYPPA or QQSHSWPFT. The provided antibody can be used for treating cancer.

The invention discloses application of a taste sense 2 receptor member 31 (TAS2R31) as a knockout target in cellular immunotherapy, and belongs to the technical field of biological medicines. Specifically, it is found for the first time that the proliferation capacity of tumor infiltrating lymphocytes (TIL cells) obtained after TAS2R31 gene is knocked out is remarkably improved, the killing capacity is remarkably enhanced, and the cell phenotype can be converted towards the direction more beneficial to anti-tumor immunity; meanwhile, the TIL cells with the TAS2R31 gene knocked out can release functional cell factors after being stimulated by antigens, and the TIL cells have definite anti-tumor immunocompetence. Therefore, the TAS2R31 is used as a new knockout target and is used for developing a new tumor treatment scheme based on TIL cells or TCR-T cells. The cell therapy provided by the invention provides a new strategy direction for tumor treatment by improving the multiplication capacity and the immune function of the TIL cells and the TCR-T cells.

The application provides a gadolinium-based composite material with microwave response heat production and double-mode imaging effect, and preparation and application thereof. The gadolinium-based composite material prepared by the application is applied to the fields of microwave hyperthermia and double-mode imaging of tumors, and has good clinical application value. The gadolinium-based composite material synthesized by the application has low cytotoxicity and good cell internalization efficiency, can significantly increase the killing effect of microwaves on tumor sites, and has higher cell internalization efficiency and better microwave heating performance through adjustment of the morphology of the gadolinium-based composite material. In addition, Gd 3+ in the nanomaterial has a nuclear magnetic resonance enhancement effect, and the loaded fluorescent dye has a fluorescence imaging effect, so that the material has double-mode imaging function and can be used as a microwave diagnosis and treatment agent to realize tumor diagnosis and treatment integration.