13 results about "Large cell" patented technology

The invention discloses double-mesoporous silica nanoparticles for modifying ionizable amino and a preparation method and application of the double-mesoporous silica nanoparticles. The core technical process of the double-mesoporous silica nanoparticles comprises the following steps: firstly, synthesizing mesoporous silica through a double-template method of a block copolymer and a surfactant; then grafting ionizable amino to the surface of the mesoporous silica through a silane coupling agent; and finally, RNA is loaded on the modified mesoporous silica by electrostatic adsorption, and efficient tumor treatment is finally realized. The invention also discloses an application of the silicon dioxide nanoparticles in RNA delivery. The silicon dioxide nanoparticles prepared according to the method disclosed by the invention have high RNA loading efficiency and cell uptake efficiency. The double-mesoporous silica nanoparticles modified with ionizable amino groups have the advantages of large drug loading capacity, high cell uptake rate, high biocompatibility, simplicity in synthesis, mild reaction conditions, convenience in cutting and the like, and have a good application prospect.

The invention discloses a stem cell-based microvesicle as well as a preparation method and application thereof, belongs to the technical field of biological tissue engineering, and particularly relates to a preparation method of the stem cell-based microvesicle, which comprises the following steps: culturing stem cells until the cell fusion degree is 80-90%, performing hypoxia treatment, and cleaning for 2-3 times; standing and culturing the cleaned stem cells, then adding a calcium ion carrier, and carrying out ultrasonic treatment; the serum-free basic culture medium containing the calcium ion carrier is immediately absorbed and removed, the cells are cleaned through PBS, culture is conducted for 24 h, and cell supernatant is collected and merged respectively; performing first centrifugation to remove cell debris; performing second centrifugation to remove dead cells and large cell debris; carrying out third centrifugation to remove organelles; fourth centrifugation is carried out, large vesicles are removed, and a final supernatant is obtained; and filtering and centrifuging to obtain a microvesicle precipitate. The preparation method of the microvesicles aims at systematically improving the yield and biological activity of the stem cell microvesicles through low-oxygen pre-stimulation, ultrasonic-calcium ion carrier synergistic induction and differential centrifugation.

According to the invention, a novel immune checkpoint molecule SIDT1 is found. The SIDT1 is a powerful T cell inhibition factor mainly expressed on CD8 < + > T cells. A series of SIDT1 inhibitors are identified in the invention. The SIDT1 inhibitor can enhance the anti-tumor CD8T cell reaction and limit tumor progression, so that a new thought is provided for treatment and prevention of related tumor patients with PD-1 treatment resistance.

This disclosure provides medicaments and methods for treating envenomation using small molecule inhibitors of secretory phospholipase A2 (sPLA2). The sPLA2 inhibitor AZD2716 and related compounds can be used as monotherapy. Alternatively, the sPLA2 inhibitor varespladib and / or methyl varespladib can be used in combination with a statin. When a subject has been envenomed (for example, by a snake bite or bee sting), the medicaments can be administered to prevent lethal effects or tissues damage cause by the venom: for example, acute kidney injury, mast cell degranulation, or cerebral edema. The medicaments may be contained in an automatic injection device or an injection pen to deliver an effective dose as soon as possible following envenomation.

The present application belongs to the technical field of nucleic acid delivery and gene editing, and particularly relates to a method for knocking out a target gene of a cell in vitro by using an LNP delivery system. In view of the technical problems of unstable editing efficiency, large difference in editing efficiency between different individuals, low transfection efficiency, large cell damage, unstable knockout effect and the like when a T cell is transfected by using an existing LNP for gene editing, the present application provides a method for efficiently knocking out a target gene of a T cell in the form of LNP by optimizing the LNP and LNP transfection operation parameters in a systematic manner. The method can effectively solve the above technical bottlenecks, realize efficient and stable knockout of a target gene of a T cell, and provide reliable technical support for T cell function research and immunotherapy application.

According to the present invention, a pharmaceutical composition for preventing and treating lung adenocarcinoma, comprising K-ras-specific activated T cells, is used as an antigen composition designed such that a K-ras mutant (G12D, G12V, and G13D) recombinant overlapping peptide is sequentially divided into a total of 12 epitopes (n=1 to 12, and the last epitope (n=12) consists of 23 amino acids) in units of 30 amino acids in the amino acid sequence of K-ras, and 15 amino acid sequences overlap between the epitopes. Thus, the pharmaceutical composition is more effective in recognizing and killing lung adenocarcinoma in which K-ras, K-ras mutant G12V, K-ras mutant G12D, or K-ras mutant G13D is detected. Therefore, according to the present invention, the pharmaceutical composition for preventing and treating lung adenocarcinoma, comprising K-ras-specific activated T cells, can be used to effectively prevent and treat lung adenocarcinoma, particularly lung large cell adenocarcinoma, in which K-ras as well as K-ras mutants are detected.

Disclosed are a delivery system based on sensitized mast cells, a preparation method therefor, and an application thereof, as well as a pharmaceutical composition and a drug administration device involving the delivery system of sensitized mast cells. The delivery system utilizes the specific recognition of tumor antigens by sensitized mast cells to targetedly deliver drugs to tumor cells, while protecting the drugs from the clearance of the circulating immune system. Sensitized mast cells rapidly degranulate under the activation of tumor antigens to release drugs, thereby enhancing infection, exerting an oncolytic effect, lysing tumor cells and releasing antigens, and activating an anti-tumor immune response. The delivery system can be used as a promising platform technology for personalized therapy.

A method for obtaining a genetically engineered leukocyte composition is provided. The method includes: (a) enriching a population of large cells from a biological sample obtained from a subject, wherein the biological sample comprises leukocytes without performing density gradient centrifugation; (b) contacting the population of large cells with an activating agent; and (c) transducing the population of large cells with a viral vector comprising a polynucleotide. The enriching comprises an array-based separation comprising a microfluidic device configured for deterministic lateral displacement comprising an array of obstacles, and the obstacles are elongated so that their length perpendicular to bulk fluid flow (P1) is longer than their width parallel to bulk fluid flow (P2) by at least 10%.

The application discloses a high-purity NKT cell preparation and a preparation method and a cryopreservation regulation method, and belongs to the fields of cell biology technology and immunotherapy. The method systematically solves multiple challenges of low purity, insufficient amplification efficiency, poor cell viability, high cost and difficulty in large-scale production of NKT cells in the prior art through a unique secondary cryopreservation process, innovative application of platelet lysate and specific induction of alpha-galactosylceramide (alpha-GalCer). The prepared NKT cell preparation has the advantages of high purity, large amplification fold, strong cell function activity and good safety, and provides a high-quality and standardized cell source for clinical applications such as tumor immunotherapy, and has great industrialization prospects.

A drug delivery system based on sensitized mast cells, its preparation method, and its application are disclosed, along with a pharmaceutical composition and delivery device involving the sensitized mast cell delivery system. This delivery system utilizes the specific recognition of tumor antigens by sensitized mast cells to target and deliver drugs to tumor cells while protecting them from clearance by the circulating immune system. Upon activation by tumor antigens, sensitized mast cells rapidly degranulate to release the drug, thereby enhancing infection response, exerting an oncolytic effect, lysing tumor cells and releasing antigens, and activating an anti-tumor immune response. This delivery system can serve as a promising platform technology for personalized therapy.

The invention discloses a synthesis method and application of tumor microenvironment GSH / pH dual response type copper-based self-assembly nanoparticles, and belongs to the technical field of nano material preparation. The preparation method comprises the following steps: self-assembling copper ions, 3, 3 '-dithio-bis-propionyl hydrazide and a copper chaperonin inhibitor DCAC50, and carrying out surface modification by using F-127, so as to obtain the copper-based self-assembled nanoparticles. The material can respond to GSH / acidic pH of TME, released Cu < 2 + > is reduced into Cu under the action of high-concentration GSH, a large amount of active oxygen is generated through a Fenton-like reaction while copper death is triggered, and oxidative stress in cells is amplified; the released DCAC50 inhibitor can block Cu efflux mediated by copper chaperonin Atox1, and copper ion outflow is inhibited. Through double regulation and control of copper metabolism kinetics, tumor cell copper death is synergistically induced, oxidative stress is enhanced, and the efficient anti-tumor effect is achieved.

Inhibiting mast cell activation by binding sialic acid-binding immunoglobulin-like lectin-9 (Siglec-9) is described. Inhibiting mast cell activation by binding Siglec-9 can be used to treat mast-cell associated inflammatory disorders, such as allergic diseases, rheumatoid arthritis, and mastocytosis.