11 results about "Chlorotoxin" patented technology

The invention provides a drug delivery system, the drug delivery system is formed by cross-linking and curing hyaluronic acid conductive hydrogel and chitosan nanoparticles modified by chlorotoxin, the hyaluronic acid conductive hydrogel is formed by cross-linking and curing hyaluronic acid-methacrylic anhydride and reduced graphene oxide, and the chitosan nanoparticles modified by chlorotoxin are formed by cross-linking and curing hyaluronic acid-methacrylic anhydride and reduced graphene oxide. The chlorotoxin-modified chitosan nanoparticles are formed by loading a therapeutic drug on chitosan nanoparticles, coupling chlorotoxin by adopting an EDC / NHS activation method, and modifying by PEG (Polyethylene Glycol). The invention also provides a preparation method of the drug delivery system. The invention also provides application of the drug delivery system in preparation of drugs for treating tumors. According to the invention, two stages of carriers are used for synergistically and doubly loading therapeutic drugs, so that the conductive function, biocompatibility, drug loading stability and release controllability are considered, and the MGMT high-expression mediated tumor drug resistance is effectively reversed.

The invention relates to chlorotoxin-melittin nanoparticles as well as a preparation method and application thereof. The method comprises the following steps: weighing chlorotoxin, dissolving the chlorotoxin in a PBS buffer solution, adding 2-imino sulfane hydrochloride, fully mixing, and incubating at room temperature to form a CTX-SH solution; the preparation method comprises the following steps: weighing dimyristoyl phosphatidylcholine, adding a trichloromethane solution, uniformly mixing, then adding a cholesterol oleate solution and a phosphatidyl ethanolamine-polyethylene glycol 2000-maleimide solution, and sufficiently and uniformly mixing; drying the solution, resuspending with a PBS (Phosphate Buffer Solution), and fully dissolving by ultrasonic; adding a thiolated CTX-SH solution into the solution, incubating for 1-3 days, and carrying out ultrafiltration purification to form a CTX-NP nanoparticle solution; preparing a melittin solution, dropwise adding the melittin solution into the CTX-NP nanoparticle solution, incubating for 10-24 hours, and performing ultrafiltration purification. The invention has the advantages of targeting brain glioma, inhibiting the growth of in-situ brain glioma and improving the immunosuppressive microenvironment of brain glioma.

The invention relates to the technical field of drug delivery carriers, in particular to chlorotoxin-melittin nanoparticles as well as a preparation method and application thereof. The preparation method comprises the following steps: weighing chlorotoxin, dissolving chlorotoxin in a PBS buffer solution, adding 2-imino sulfane hydrochloride, fully mixing, and incubating at room temperature to form a CTX-SH solution; the preparation method comprises the following steps: weighing dimyristoyl phosphatidylcholine, adding a trichloromethane solution, uniformly mixing, then adding a C.O solution and a phospholipid-polyethylene glycol-maleimide solution, and sufficiently and uniformly mixing; drying the solution, resuspending with a PBS (Phosphate Buffer Solution), and fully dissolving by ultrasonic; adding a thiolated CTX-SH solution into the solution, incubating for 1-3 days, and carrying out ultrafiltration purification to form a CTX-NP nanoparticle solution; preparing a melittin solution, dropwise adding CTX-NP, incubating for 10-24 hours, and performing ultrafiltration purification. The invention has the advantages of targeting brain glioma, inhibiting the growth of in-situ brain glioma and improving the immunosuppressive microenvironment of brain glioma.

The invention provides a bacterial outer membrane vesicle as well as a preparation method and application thereof. Mediated cell-penetrating peptide and chlorotoxin are co-expressed on the surface of the bacterial outer membrane vesicle. The polypeptide can efficiently pass through BBB and specific targeting tumor cells in vitro and in vivo, and ferroptosis of tumor cells is induced by stimulating IFN-gamma released by CD8 + T cells in vivo, so that growth of glioblastoma is remarkably inhibited. In addition, the IFN-gamma enhances the ferroptosis of the tumor cells caused by the ferroptosis inducer RSL-3 and the erastin. The invention further provides a pharmaceutical composition, the RSL-3 is loaded to the OMV-C-C (at) RSL-3 nano delivery system formed by OMV-C-C, and the OMV-C-C and the RSL-3 show a good synergistic effect in the aspect of inhibiting the growth of glioblastoma.

Described are γδ T-cells that express a multivalent CLTX-CAR and also express a survival factor, a population of the γδ T-cells that express a multivalent CLTX-CAR and the survival factor, pharmaceutical compositions thereof, and methods of treating cancer or a tumor in a subject comprising administering to a subject an effective amount of the multivalent CLTX-CAR γδ T-cells and co-administering a chemotherapeutic agent, e.g., the chemotherapeutic agent to which the survival factor confers resistance.

Compositions, formulations and kits comprising chlorotoxin conjugate compounds are provided, including native and modified variants of chlorotoxin peptide conjugated to reporter molecules including fluorescent dyes. Methods of detecting and treating cancers and tumors with chlorotoxin conjugate compounds are also provided, including methods of imaging tumor tissues and cells. Dosing and pharmacokinetic profiles for therapeutic and diagnostic applications using chlorotoxin conjugate compounds are also provided.

The application belongs to the technical field of biological medicine polypeptide, and particularly relates to a polypeptide conjugate of chlorotoxin analog and application thereof in preparation of a medicine for preventing, treating and curing cancer related diseases. The polypeptide conjugate of chlorotoxin analog is shown as formula (I). The polypeptide drug conjugate of chlorotoxin analog provided by the application improves the solubility of the medicine, has the characteristics of high activity, strong specific binding with a target, obvious intracellular endocytosis, and the ability of increasing the penetration of the medicine through the blood-brain barrier.

The invention discloses a fusion protein of a targeted specific antigen GPC3 and application thereof, and relates to the technical field of biological medicine, the fusion protein comprises an IPA structural region and a Cltx structural region; the IPA is a GPC3 C terminal targeting peptide, and the Cltx is chlorotoxin. A prokaryotic expression vector pET-32a-TrxA-IPA-Cltx is designed, soluble expression is achieved in escherichia coli, and the recombinant protein with electrophoresis-grade purity is obtained through purification. In-vitro experiments prove that the fusion protein has no significant inhibition effect on the cell viability of HL-7702, but can significantly inhibit the cell viability of liver cancer cells HepG2, Hep3B and MHCC97H and induce cell apoptosis. The IPA targeting domain is combined with the antitumor function of Cltx for the first time, a new strategy is provided for targeted therapy of GPC3 high-expression hepatoma carcinoma cells, and clinical application potential is achieved.

The invention discloses a fusion protein of a targeted specific antigen MUC16 and application thereof, and relates to the technical field of biological medicines, the fusion protein Cltx-M64 is constructed by fusing 64 amino acid domains at the N end of mesothelin with an anti-tumor functional domain of chlorotoxin by utilizing the high affinity targeting characteristic of the 64 amino acid domains at the N end of the mesothelin. By designing a prokaryotic expression vector pSYPU-1b-Cltx-M64, soluble expression is realized in escherichia coli, and the recombinant protein with electrophoresis-grade purity is obtained through purification. In-vitro experiments prove that the fusion protein can significantly inhibit pancreatic cancer AsPC-1 cell viability and induce cell apoptosis, and the action mechanism of the fusion protein is related to targeted MUC16 mediated endocytosis and downstream signal channel regulation. The M64 targeting domain is combined with the antitumor function of Cltx for the first time, a new strategy is provided for targeted therapy of MUC16 high-expression pancreatic cancer, and clinical application potential is achieved.

The present disclosure relates to a recombinant expression vector for secretion of chlorotoxin and an attenuated Salmonella strain transformed therewith, and provides: a recombinant expression vector comprising a flgM gene and a chlorotoxin gene; an attenuated Salmonella strain transformed therewith; and a pharmaceutical composition for cancer treatment, comprising the attenuated Salmonella strain.

The invention provides chimeric antigen receptor(s) (CAR(s)) that comprise a fusion protein of CTX or any functional variant thereof or a CTX-like peptide or any functional variant thereof as the extracellular antigen recognition moiety of the CAR. CAR(s) comprising CTX, a CTX-like peptide or functional variants of the foregoing are collectively referred to herein as “CTX-CAR(s).” Such CTX-CAR(s) may further comprise additional moieties or domains in the extracellular domain, a transmembrane domain and at least one intracellular signaling domain. Such CTX-CAR(s) may be expressed in a host cell, such as, but not limited to, an immune effector cell. The present invention also provides methods of treatment (such as, for example, methods for treating cancer) by providing to the patient in need thereof immune effector cells that arc engineered to express a CTX-CAR described herein.