102 results about "Dual targeting" patented technology

The present invention relates to: a dual targeting antibody of a novel form having a water-soluble ligand fused to the N-terminus of a heavy chain or light chain of an antibody; a DNA encoding the dual targeting antibody; a recombinant expression vector containing the DNA; a host cell which is transformed with the recombinant expression vector; a method for preparing the dual targeting antibody by culturing the host cell; and a pharmaceutical composition including the dual targeting antibody.

The invention relates to dual-targeting ursolic acid (UA) / siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application. The technical scheme of the invention lies in that 1, fluorescently-labeled mesoporous silica dioxide nano particles are synthesized through the template method; 2, the surface of FMSN is subjected to amino modification through 3-aminopropyltriethoxysilane; 3, ursolic acid (UA) and siRNA are jointly loaded into porous channels of the nano particles; 4, hyaluronic acid is loaded into the outer surfaces of the nano material in a wrapping manner through electrostatic absorption, so as to obtain the dual-targeting ursolic acid (UA) / siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid nano particles. According to the dual-targeting ursolic acid (UA) / siRNA loaded fluorescent mesoporous silica dioxide-hyaluronic acid and application, the prepared nano material is uniform in particle size distribution, and good in dispersibility, the stability of siRNA can be improved, and besides, siRNA can further specifically target tumor cell surface adhesion molecules like ICAM and CD44, therefore the anti-tumor effect of drugs can be greatly improved, and the toxic and side effect of the drugs can be further reduced.

The present invention relates to dual-targeting cytotoxic compounds of formula (I) and to their preparation. The described compounds are endowed with tumour specific action, incorporating three functional units: a tumour recognition moiety and a tumour selective enzymatic substrate sequence connected together by means of a spacer. These conjugates are designed to guarantee serum stability and, at the same time, the desired action inside the tumour cells as a result of enzymatic cleavability. [(L-D)nE]m-F-D-PI-SI-CT Formula (I).

The invention relates to a preparation method of a dual-targeting drug carrier based on a magnetic metal organic framework material, belonging to the technical field of preparation of bio-medicinal functional materials. The preparation method comprises the following steps: firstly, modifying ferroferric oxide to form dopamine-wrapping ferroferric oxide, and preparing the dual-targeting drug carrier based on the magnetic metal organic framework material by taking dopamine-wrapping ferroferric oxide (Fe3O4@PDA) as the matrix material; and carrying out a series of treatment to obtain an adsorbent, and carrying out selective recognition and separation on adriamycin in an aqueous solution by adopting the adsorbent. The dual-targeting drug carrier based on the magnetic metal organic framework material prepared by adopting the method provided by the invention has good heat stability and very large medicine-carrying capacity, has the acid-base effect, and also has the function of controlling medicine release.

Methods, compounds, and compositions for treating a proliferative disorder or other physiological conditions via a dual targeting anticancer therapy are provided. In some embodiments, a dual targeting anticancer therapy may utilize a composition comprising a platinum agent. The platinum agent may comprise a precursor to a therapeutically active platinum compound and at least one precursor to a vitamin E agent. The vitamin E agent may target cancer cells via a different mechanism of action than the therapeutically active platinum compound resulting in a dual targeting anticancer agent. The method of treatment may involve administering to a patient the dual targeting anticancer agent. Following administration, a therapeutically active platinum compound and a vitamin E agent may form at the physiologically relevant site. In some embodiments, administering a platinum agent comprising precursors of therapeutically active agents may be more effective than individually or simultaneously administering separate molecules of those therapeutically active agents.

The invention discloses a folate-targeted hydrophobic medicine-loaded polymeric vesicle and a preparation method and use thereof. The polymeric vesicle is prepared by the following steps of: (1) dissolving amphiphilic triblock copolymer and a hydrophobic medicine in an organic solvent, adding distearamide phosphatidyl ethanolamine-polyethylene glycol (2000) folate, evaporating to remove the organic solvent to prepare a uniform thin film, blowing and drying; and (2) adding double distilled water and products in the step (1) into a container, hydrating, shaking and uniformly mixing to ultrasonically form stable emulsion, performing film filtering, collecting filter liquor and performing freeze drying, The polymeric vesicle has main advantages of liposome, nanoparticles and other particle medicine-loaded systems, stability in vivo and in vitro obviously superior to the liposome, thicker film layer, contribution to encapsulating the hydrophobic medicine, dual-targeting function of EPR passive targeting and folate active targeting, and capacity of making the medicine-loaded vesicle effectively targeted and gathered on a tumor part and fulfilling the aim of targeted therapy.

The invention discloses a dual-targeting ultrasonic contrast agent and a preparation method thereof. The contrast agent is an Integrin alpha v beta 3 / MCP-1 dual-targeting micro-vesicle, the dual-targeting micro-vesicle comprises a lipid shell and a gas inner core, and the external surface of the lipid shell is connected with an Integrin alpha v beta 3 monoclonal antibody and an MCP-1 monoclonal antibody. Through the combined application of different target spots, the targeting efficiency of the contrast agent can be effectively increased, and the degree of enrichment of the carrying genes in the target tissue can be greatly increased. In addition, the contrast agent disclosed by the invention is an ultrasonic contrast agent with double functions of development and treatment, and tumor images can be accurately observed in real time through an ultrasonic imaging system; and after gene transfection is realized through high-strength ultrasonic irradiation, the tumor gene treatment effect can be achieved.

The invention discloses a folic acid mediated antitumor drug superparamagnetic tumor targeted nanoparticle. A superparamagnetic iron oxide nanoparticle is adopted as the carrier, and high temperature thermal decomposition method is employed to synthesize polyethylene glycol-polyethyleneimine modified uperparamagnetic iron oxide nanoparticle, then a folic acid ligand is grafted on the surface of iron oxide by chemical method, and then an antitumor drug is loaded into the iron oxide nanoparticle by electrostatic adsorption and hydrogen bonding, thus obtaining the folic acid mediated antitumor drug superparamagnetic tumor targeted nanoparticle. According to the invention, the dual targeting effect can strengthen the anti-tumor effect of the antitumor drugs, and the folic acid mediated antitumor drug superparamagnetic tumor targeted nanoparticle has small toxic and side effect, thus being a tumor treatment nanoparticle preparation with substantial development value.

The invention belongs to the field of biomedicine. In particular, the invention discloses paclitaxel nano liposomes of dual targeting tumor. The dual targeting paclitaxel nano liposomes consist of three parts: polypeptides of dual targeting tumor, lipid attachments and paclitaxel liposomes. The invention also discloses a method for preparing the paclitaxel nano liposomes of dual targeting tumor and application of paclitaxel nano liposomes to preparation of a tumor-inhibiting medicament.

The invention discloses an enhanced type anti-tumor NK cell and a preparation method and application thereof. The anti-tumor NK cell is an NK cell modified by a dual-targeting chimeric receptor, and the dual-targeting chimeric receptor is composed of a PD-1 extracellular domain, an NKG2D full-length domain and a costimulatory molecule 41BB intracellular domain. The anti-tumor NK cell disclosed bythe invention has the advantages that by adopting the dual-targeting chimeric receptor for modifying the NK cell, the anti-tumor treatment effect of the NK cell can be improved, specific recognition and killing of solid tumors can be realized, and excessive immune response of an organism can not be caused.

The present invention discloses dual-targeting fusion protein CFmDEC capable of mediating a type 5 adenovirus vector to be specifically bound with a surface molecule DEC205 of a dendritic cell; and by utilizing a gene fragment sig-tG250-Fc-IRES-GM-CSF-B7.1(25) of a multi-targeted anti-renal cancer compound antigen, an anti-renal cell carcinoma adenovirus vaccine-Ad5-tG250FcGB is constructed with a type 5 replication-deficient adenovirus as a vector. The dual-targeting fusion protein CFmDEC is capable of enhancing the antitumor effect of the renal cell cancer adenovirus vaccine Ad5-tG250FcGB, is effectively combined with the adenovirus, improves the DCs-targeted ability of the adenovirus vaccine, and can induce higher specific antitumor immune response in a human body and suppress the growth of renal cell cancer.

The present invention provides a method of treating or preventing cardiac disorders in a subject in need thereof by inhibiting the expression or function of both miR-499 and miR-208 in the heart cells of the subject. In particular, specific protocols for administering inhibitors of the two miRNAs that achieve efficient, long-term suppression are disclosed. In addition, the invention provides a method for treating or preventing musculoskeletal disorders in a subject in need thereof by increasing the expression or activity of both miR-208 and miR-499 in skeletal muscle cells of the subject.

Methods are provided for targeting cells for depletion, including without limitation cancer cells, in a regimen comprising contacting the targeted cells with a combination of agents, including (i) an agent that blockades CD47 activity; and (ii) an antibody that specifically binds to EGFR. In some embodiments the cancer cells have a mutated form of one or more of KRAS, NRAS or BRAF. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used.

The invention belongs to the field of tumor biological products, in particular to a chimeric antigen receptor and its gene and a recombinant expression vector, CD19-CD20 dual targeting T cells and anapplication thereof. The chimeric antigen receptor is CD20ScFv-L-CD19ScFv-CD8-CD137-CD3 zeta, which includes CD20ScFv, ligation peptide L, CD19ScFv, a hinge region and a transmembrane region of CD8, an intracellular signal domain of CD137, and an intracellular signal domain of CD3 zeta which are connected in series in order. In the treatment of B cell line hematological malignancy, the chimeric antigen receptor-modified T cells of the present invention can not only specifically recognize tumor cells expressed by a single target of CD19 antigen or CD20 antigen, but also to recognize tumor cellsco-expressed by two targets of CD19 antigen and CD20 antigen, compared with single target CAR T, dual-target CAR T has stronger anti-tumor activity, which avoids immune escape of tumor cells with lowabundance antigen expression, and the risk of recurrence is reduced.

The invention discloses a dual-targeting delivery method of pectin nanoparticles modified by folic acid. The pectin nanoparticles are prepared by the following steps: performing conjugated combinationof pectin and eight-arm polyethylene glycol, connecting the pectin with the folic acid through an amido bond, combining the eight-arm polyethylene glycol with an anti-cancer drug ursolic acid throughan ester bond to obtain a folic acid-(pectin-multi-arm polyethylene glycol)-ursolic acid prodrug, and mixing the folic acid-(pectin-multi-arm polyethylene glycol)-ursolic acid prodrug with an anti-cancer drug hydroxycamptothecine in a certain proportion so as to prepare dual-targeting nanoparticles with a core-shell structure through a self-assembly method. The dual-targeting pectin nanoparticlesprepared by the method have good biocompatibility, the pectin can be degraded by pectinase of the colon, the eight-arm polyethylene glycol is a nontoxic carrier, a burst release phenomenon does not occur in an in vivo transport process of drugs, and an in vitro release test shows good pH value responsivity. A prepared nano drug is high in drug loading rate, controllable in embedding rate and highin yield; and as a novel drug carrier, the pectin has good clinical application prospect.

The invention provides a specific dual-targeting antibody as well as a preparation method and application thereof. The specific dual-targeting antibody comprises a first antigen binding structural domain specifically bonded with human CD3, and a second antigen binding structural domain specifically bonded with a cMet antigen, and is capable of specifically identifying and bonding tumor cells with overexpression of the cMet antigen, wherein the tumor cells are of liver cancer, other cMet-positive tumor diseases and the like; furthermore, the specific dual-targeting antibody is also capable of bonding a T cell receptor, and mediates T cells to play a killing role, thus clearing cMet infection; therefore, the specific dual-targeting antibody has a great application value in diagnosis, treatment, prevention and detection of cMet-related diseases. The invention also provides microcircular deoxyribonucleic acid (DNA) encoding the nucleotide sequence of the specific dual-targeting antibody. The specific dual-targeting antibody and the microcircular DNA which are provided by the invention can be used for preparing antibody-based pharmaceutical compositions or cMet-positive tumor cell diagnostic reagents.

The present invention provides a method of treating or preventing cardiac disorders in a subject in need thereof by inhibiting the expression or function of both miR-499 and miR-208 in the heart cells of the subject. In particular, specific protocols for administering inhibitors of the two miRNAs that achieve efficient, long-term suppression are disclosed. In addition, the invention provides a method for treating or preventing musculoskeletal disorders in a subject in need thereof by increasing the expression or activity of both miR-208 and miR-499 in skeletal muscle cells of the subject.

The present invention relates complexes comprising a PSMA targeting compound linked to a radionuclide, such as 212Pb or 227Th. These compounds, and pharmaceutical compositions comprising them, can be used for medical applications. These applications include the treatment of prostate cancer, and the complexes allow for dual targeting of cancers.

The invention discloses a preparation method of tumor-targeting aptamer-modified drug gene co-transport nanoparticles and application of the nanoparticles in preparation of EGFR-mutation-resistant drugs for lung cancer. The preparation method comprises the specific steps that firstly, Apt carboxyl is activated first and then reacted with amino on the surface of PAMAM, an Apt-PAMAM carrier is synthesized, the drug ERL is encapsulated to form an Apt-PAMAM / ERL nano-drug, and the Apt-PAMAM / ERL nano-drug is compounded with SUV to form a tumor-targeting nano-composite. By means of the composite, thedefect that the ERL is poor in water solubility is overcome, and meanwhile, the surface-modified Apt and ERL dual-targeting EGFR mutation tumor cells are utilized so as to increase targeting of tumortissue; through compounding with the SUV, expression of anti-apoptosis genes is silenced, the drug resistance of the cells to the ERL is reversed, therefore, the bioavailability of the drug is effectively improved, and the clinical application value of the drug is improved.

The invention relates to combinations of FGFR1c antagonists with agonist peptides and provide dual targeting proteins which bind to FEFR1c comprising an antigen binding protein which is capable of binding to FGFR1c and which is linked to one or more agonist peptides, methods of making such constructs and uses thereof, particularly in treating obesity.

The invention provides a chimeric polypeptide with dual-targeting function, and a preparation method and applications thereof. The chimeric polypeptide of the invention comprises three sequences with the following characteristics: sequence 1 is an amino acid sequence comprising the first 20-80 human lysozyme proteins counting from end N; sequence 2 is an amino acid sequence of Exendin-4 proteins; and sequence 3 is a connecting sequence of the sequence 1 and the sequence 2 and comprises a thrombin restriction enzyme site and a dipeptidyl peptidase restriction enzyme site. The chimeric polypeptide can be synthesized by using a polypeptide synthesizing technology, or can be obtained by constructing an expression carrier comprising the polypeptide nucleotide sequence specified by the code, expressing in a genetic engineering stain and finally purifying. The chimeric polypeptide of the invention has obvious dual-targeting activity for resisting AGEs and reducing blood sugar, and can be used for preparing medicines for resisting AGEs and / or lowering high blood sugar.

The invention relates to a water bottom sludge sampling device driven by two positioning slide blocks. The water bottom sludge sampling device comprises a power mechanism, a left and right side surface positioning mechanism, a bottom positioning mechanism and a scraper pan mechanism, wherein the power mechanism and the bottom positioning mechanism are respectively mounted on at the upper part andlower part of the left and right side surface positioning mechanism, slide blocks are positioned by guide slots to vertically move in the left and right side surface positioning mechanism, shear forksare controlled by a lead screw and springs between two ends of the shear forks, and the bottom of the device is positioned by the bottom positioning mechanism. According to the device, the positionedlead screw is moved up and down by virtue of a spring force and a tensile force of a digging rope to drive the two shear forks to move so as to open or close a scraper pan, thereby finishing the sampling of water bottom sludge; the manual operation is replaced with a mechanical method, so that the amount of labor is reduced, and the interference of water flow in the water bottom can be avoided; and by arranging the springs in the shear forks, the scraper pan can be automatically opened during sinking and can be closed by overcoming an elastic force when being pulled upwards, so that the operation is simple, and the structure is elaborate.

Methods are provided for targeting cells for depletion, including without limitation cancer cells, in a regimen comprising contacting the targeted cells with a combination of agents, including (i) an agent that blockades CD47 activity; and (ii) an antibody that specifically binds to EGFR. In some embodiments the cancer cells have a mutated form of one or more of KRAS, NRAS or BRAF. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used.

The invention relates to the technical field of medicines, and discloses a dual-targeting delivery chemotherapeutic drug nanosystem, and a preparation method and an antitumor enhancement application. The drug carrier of the dual-targeting delivery chemotherapeutic drug nanosystem adopts temperature-sensitive poly(N-isopropylacrylamide) as a core and positively charged polyethyleneimine as a shell; the loaded chemotherapeutic drug is 5-fluorouracil; and the drug carrier is connected with an anti-Her-1 antibody through maleimide-polyethylene glycol-succinimide acetate. An experiment result of the dual-targeting delivery chemotherapeutic drug nanosystem shows that the dual-targeting delivery chemotherapeutic drug nanosystem has good biocompatibility, and compared with free drugs, the dual-targeting delivery chemotherapeutic drug nanosystem has the advantages of enhancement of enrichment of drugs in tumor positions, enhancement of the antitumor effect and great reduction of the toxic and side effects of chemotherapeutic drugs through an EPR effect, temperature sensitivity and antibody multiple targeting.

The invention, belonging to the field of biotechnology, relates to a brain tumor targeting gene delivery composite modified by low density lipoprotein receptor associated protein ligand polypeptide. The brain tumor targeting gene delivery composite has a dual targeting effect of BBB and glioma. Therapeutic genes can express and kill tumor cells in glioma cells, and can release gene product TRAIL protein into the environment outside the cells to combine with tumor cells by the means of cell paracrine after expressing in BCECs and then have a killing effect, thus aiming at the infiltrative growth characteristic of glioma in the brain, the brain tumor targeting gene delivery composite can kill the main glioma and simultaneously effectively inhibit the diffusion of scattered tumor cells.

A dual targeting drug carrier is provided. The dual targeting drug carrier comprises a first targeting molecule and a second targeting molecule, wherein the targeting molecule comprises peptide, protein or antibody. The targeting molecule can bind to specific receptors, proteins, or glycoproteins to recognize the specific tumor cells, tissues, or organs. The dual targeting drug carriers are further conjugated with imaging agents, radioactive molecules (radiopharmaceuticals, isotopes, or chemotherapeutic drugs) or nanoparticles to form a conjugate

The present invention discloses a dual-targeting drug carrier and a method for fabricating the same, wherein WGA- and FA-modified MPEG-PLA nanoparticles of the carrier enable the anticancer drugs encapsulated thereinside to pass through BBB and target human glioblastoma cells. The dual-target drug carrier is fabricated in an emulsion-solvent evaporation technology and verified with an in-vitro BBB model formed of HBMECs, HAs and HBVPs. The present invention can increase the permeability of the in-vitro BBB model to the dual-target drug carrier and promote the glioblastoma-inhibition effect. Therefore, the present invention would contribute to the clinical therapy of brain cancers substantially in the future.

The present invention discloses a novel lipid material for realizing transfer of triple negative breast cancer targeted drugs. The novel lipid material takes lysine as a connecting group to respectively connect a cholesteric part, a fructose part and an RGD part. Affinities between fructose in the novel lipid material and a fructose transporter GLUT5, and between RGD in the novel lipid material and an integrin receptor alpha v beta 3 are respectively utilized to realize double targeting functions of the triple negative breast cancer and exert stronger targeted treatment effects on the triple negative breast cancer. The novel liquid material can be sued for different dosages of liposomes, nanoparticles, micelle, etc. A prepared paclitaxel-loaded liposome has obvious triple negative breast cancer targeting property and a wide application prospect.

The invention relates to a supramolecular photothermal agent compound with stimuli-responsiveness as well as a composition and application thereof, and provides a micro-nano structure which is formed by self-assembling a structure shown in a formula (I), a formula (II) or a formula (III) or an isomer, a pharmaceutically acceptable salt, a hydrate or a solvate of the structure in a water solution. The invention also relates to a pharmaceutical composition thereof and application of the pharmaceutical composition in preparation of double-targeted light treatment drugs, preparation of drugs for diagnosing and / or treating cancers and stimuli-responsive release drugs. The compound provided by the invention can be enriched in tumor tissues through passive and active dual targeting, and can release a photo-thermal agent under pathological stimulation response of a tumor microenvironment; the compound has the advantages of higher photothermal conversion efficiency, excellent photothermal stability and fluorescence imaging, and has a good effect and small trauma when being used for in-vivo cancer phototherapy. The compound has great market value and wide economic prospect.

The invention provides a specific dual-targeting antibody, a method thereof and applications. The specific dual-targeting antibody has a first antigen binding domain which binds to human CD3 specifically and a second antigen binding domain which binds to an EGFRvIII antigen specifically, can recognize and bind to the EGFRvIII antigen and EGFRvIII over-expressed cancer cells specifically, and can bind to a T cell receptor (TCR), wherein cancers comprise a liver cancer, other EGFRvIII positive tumor diseases and the like; and the specific dual-targeting antibody mediates a T cell to play a killing role, thus EGFRvIII infection is removed, and the specific dual-targeting antibody has great application value in diagnosis and treatment, prevention, and detection of EGFRvIII related diseases. The invention also provides a minicircle DNA which has a nucleotide sequence for coding the specific dual-targeting antibody. The invention provides the specific dual-targeting antibody and the minicircle DNA, wherein the specific dual-targeting antibody and the minicircle DNA can be used for preparing an antibody pharmaceutical composition or preparing an EGFRvIII positive tumor cell diagnostic reagent.