60 results about "Nucleolin" patented technology

The present invention provides a method for inhibiting the proliferation of malignant and / or hyperplastic cells in a subject by administering to the subject a therapeutically effective amount of a guanosine rich oligonucleotide. The present invention also provides oligonucleotides which are capable of being specifically bound to a specific cellular protein which is nucleolin and / or nucleolin-like in nature, which is implicated in the proliferation of cells, specifically malignant and / or hyperplastic cells, and a method for their selection.

The invention discloses a method for preparing a meso-porous silicon nano medicine carrier with cell specificity target, reduction responsiveness and triple anticancer treatment effects. The method comprises the following steps: firstly, synthesizing meso-porous silicon nano particles by using a gel dissolution method, subsequently, introducing a disulfide bond onto the surface of a meso-porous silicon nano reservoir by using a chemical modification method, innovatively fixing cytochrome C with an apoptosis-inducing function onto the surface of the meso-porous silicon nano reservoir, blocking meso-porous channels with medicines, finally modifying DNA (Deoxyribose Nucleic Acid) aptamer single chain molecules (AS1411, with a cancer cell apoptosis-inducing function) onto the surface of a meso-porous silicon / cytochrome C nano composite system, and taking the system as specificity ligand of a receptor (nucleolin protein) which is overexpressed on the surface of liver cancer cytomembrane, thereby establishing a multifunctional composite type nano medicine carrier system for achieving triple anticancer treatment under combined action of medicines, blocking substances and target molecules inside meso-pores.

The present invention provides for methods of producing human monoclonal antibodies to human nucleolin, cells producing such antibodies, and the antibodies themselves. Also provided are methods of using the antibodies in diagnosing and treating malignant and non-malignant diseases wherein cells that express nucleolin on the cell surface contribute to the pathophysi-ology of the disease.

Improved G-rich oligonucleotide (GRO) aptamers specific to nucleolin, a method of preparing the aptamers, and a use of the aptamers for diagnosing and / or treating a nucleolin-associated disease, are provided.

The present invention provides for diagnostic kits for identifying cancer patients who are more susceptible to cancer therapies employing endostatin and other angiogenesis inhibitors, based upon the discovery that Nucleolin is a specific receptor for Endostatin. In particular, the diagnostic kits include antibody molecules against Nucleolin, DNA or RNA molecules that specifically bind to nucleic acid molecules encoding Nucleolin. The present invention also discloses methods of screening for angiogenesis inhibitors which specifically interact with Nucleolin, and act as angiogenesis inhibitors in an analogous manner as Endostatin. In addition, the present invention discloses methods of inhibiting the proliferation of endothelial cells or angiogenesis of tumor by administering an anti-nucleolin antibody linked to a cytotoxic agent such as tumor necrosis factor alpha to the endothelial cells.

The present invention relates to novel methods for modulating the activity of p53 tumor suppressor protein by affecting p53 translational regulation. More specifically, the invention relates to novel methods for modulating p53 mRNA translation in a cell by affecting a function of a p53 5′-untranslated region (5′UTR), including its interaction with proteins such as Ribosomal Protein L26 (RPL26), nucleolin, and p53. The invention also relates to the use of these methods for treating cancer, neurodegenerative disorders and minimizing the negative effects of cellular stresses.

Hydrophobic nanoparticles have great potential in biological analysis and biomedical application. The invention provides a simple method; a DNA nanostructure is used as a phase transition reagent; the DNA nanostructure is a DNA tetrahedral structure formed by self-assembly of four single-stranded DNAs, tail ends of three single-stranded DNAs of the four single-stranded DNAs are modified by carboxyl, the other one single-stranded DNA contains an aptamer, and the aptamer can be specifically combined with highly expressed nucleolin on a cancer cell membrane surface, so that the targeting ability of the nanoparticles is increased and the cell uptake ability is improved. The DNA tetrahedron as the phase transition reagent is non-toxic and convenient and only requires simple separation, and the high-stability and good-dispersion hydrophilic nanoparticles can be prepared.

Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and / or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

The invention relates to nucleolin binding peptides, nucleolin binding peptides and anti-nucleolin antibody conjugates with cytotoxic activity, fusion constructs, methods of using nucleolin binding peptides and antibodies and fusion constructs thereof, and methods of treating various disorders, undesirable conditions and diseases treatable with nucleolin binding peptides and fusion constructs, such as undesirable or aberrant cell proliferation (hyperproliferation) or hyperproliferative disorders, including tumors, cancers, neoplasia and malignancies, angiogenesis related or dependent diseases, and inflammatory diseases and inflammation.

The invention discloses an environmental pH stimuli-responsive type tumor targeting and controlled drug release nano-carrier and a preparation method of the nano-carrier. Dendrimer macromolecular nano-polymer material PAMAM (polyamidoamine) is taken as a main body of a structure and connected with an amphiphilic block copolymer PEG (methoxy polyethylene glycol)-PLA (poly-l-aspartic acid), DOX (doxorubicin) is covalently conjugated to a hydrophobic fragment, namely, PLA, of an arm of the amphiphilic block copolymer and is connected though a pH sensitive hydrazone bond, so that a system has thecharacteristic of in-vivo smart drug release, and drug release can be controlled by in-vivo pH. The connection with a F3 polypeptide nucleolin targeting ligand is realized through a hydrophilic PEG chain segment, and tumor targeting of the system is realized in specific uptake of tumor and nuclear localization. The nano-carrier has potential clinical application value, and powerful technical support is provided for treatment of other types of malignant tumor cells.

Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic; hyperproliferative, and / or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and / or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

Provided are an isolated nucleolar protein having an amino acid sequence of NCBI GenBank Accession No. XP_033371, a method of diagnosing colorectal cancer in an individual, including measuring an expression level of a protein having an amino acid sequence of NCBI GenBank Accession No. XP_033371 in the individual, and a polynucleotide for diagnosis or treatment of colorectal cancer including at least 10 contiguous nucleotides of a nucleotide sequence selected from the group consisting of nucleotide sequences of SEQ ID NOS: 1-5 and including a nucleotide at position 101 of the nucleotide sequence, or a complementary polynucleotide thereof.

The invention relates to a copper phthalocyanine molecule-based detection, imaging and treatment integrated nanoprobe. The copper phthalocyanine molecule-based detection, imaging and treatment integrated nanoprobe comprises hexagonal boron nitride nanosheets, copper phthalocyanine molecules and two groups of oligonucleotide binding sequences. One end of each of the two groups of oligonucleotide sequences designed by the invention is a base pair for detecting and circularly amplifying microRNA-21, and the other end is an AS1411 sequence. The AS1411 sequence not only can recognize nucleolin highly expressed on the surfaces of tumor cells to play a role in targeted localization, but also can carry copper phthalocyanine molecules with poor water solubility based on a G quadruplex formed underspecific conditions, then, the nucleotide sequence loaded with copper phthalocyanine is adsorbed on the surfaces of the hexagonal boron nitride nanosheets through pi-pi accumulation to enter tumor cells. The invention further discloses application of the copper phthalocyanine molecule-based detection, imaging and treatment integrated nanoprobe in diagnosis and treatment of tumor cells and living bodies. The diagnosis and treatment integrated nanoprobe can perform in-situ Raman diagnosis on tumor cells, is high in sensitivity and specificity, can realize photodynamic therapy at the same time, and has a certain application value in biological medicine and clinical diagnosis and treatment.

The invention provides a DNA nano-material, and a preparation method and an application thereof, and belongs to the technical field of nano-materials. A DNA nano-stripe band is designed on the basis of a DNA origami theory, the nano-stripe is characterized in that a rolling circle amplification reaction product obtained through rolling circle reaction amplification of a ring template with a special structure is self-assembled to form a DNA nano-crystal lattice, and the DNA nano-crystal lattice is modified with an AS1411 aptamer of targeted nucleolin to form a DNA nano-material DNA nanostripe crystal lattice band-AS1411 compound; and the DNA nano-strip crystal lattice band-AS1411 compound is combined with nano-gold balls to form the DNA nano-material nano-gold-DNA nano-crystal lattice bandcompound. The prepared DNA nano-material has wide application values in tumor diagnosis and treatment as a targeting drug carrier.

Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and / or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

Compositions and methods for modulating tumor proliferation in an individual are provided. The methods employ nucleolin-binding agents, such as aptamers. The aptamers of the present invention can be used to modulate the proliferation of malignant, dysplastic, hyperproliferative, and / or metastatic cells through interference with molecular interactions and functions of nucleolin in the tumor cell.

The invention relates to a targeted antitumor complex based on ricin, a preparing method thereof and applications of the complex. The complex is prepared by compositing carbon quantum dots and a ricinA chain to form a carbon quantum dot-ricin A chain complex, then encapsulating the complex with the lipidosome, and modifying the lipidosome with a nucleolin nucleic acid aptamer. The prepared complex can enter cells more easily, acts on ribosome through a Golgi apparatus path, has higher cytotoxicity, can effectively protect the A chain from being enzymatically decomposed by lysosome, utilizes specificity of the nucleolin nucleic acid aptamer, can be targeted on a tumor cell, reduces toxic and side effects on normal cells, and is of great importance for targeted treatment on tumor cells.

The invention relates to the technical field of plant genetic engineering, and particularly discloses application of a ZmNuC gene and an encoded protein thereof in resistance to the maize rough dwarf disease. The invention finds for the first time that the expression level of the corn nucleolin gene ZmNuC is in negative correlation with the resistance of corns to the rough dwarf disease; a new way for exploring and creating a new material for resisting to the corn rough dwarf disease is provided; a genetic material foundation is laid for subsequent research; and a good information platform is provided for the resource reservation of the corn rough dwarf disease resistant gene. The research on the rough dwarf disease resistance genetic mechanism and the disease-resistant molecular breeding of plants is promoted; and reliable material and data support is provided for the research on the molecular biology mechanism for enhancing the rough dwarf disease resistance of the plants such as corns and the like.

The invention discloses specific nucleotide of human ribosomal protein molecules hRrp15p. The nucleotide comprises a) a nucleotide sequence shown as SEQ ID NO: 1 or a complementary DNA sequence thereof, and b) a nucleotide sequence formed by deletion, substitution or insertion of one or more bases in the a) and still having nucleotide function, wherein the full length of the nucleotide shown as SEQ ID NO: 1 is 849 bases. The amino acid sequence such as SEQ ID NO: 2 corresponding to the nucleotide sequence has 282 amino acids. Polyclonal antibodies of hRrp15p are prepared, and multiple mutants of the protein molecules are constructed; and intracellular expression of the hRrp15p, sub-cellular positioning and influence of the protein molecules on nucleolin nucleolus positioning are deeply researched. Therefore, the problem hollow to position the nucleolin in a nucleolus structure is solved, the formation of the nucleolus structure is promoted, and morphological basis is laid for exertion of functions of the nucleoli in cells.

The invention belongs to the technical field of nano-drug delivery systems, and specifically relates to a subcellular targeted nano-drug delivery system. For problems in the prior art that an antitumor drug synergistic delivery system is hard to realize subcellular targeting, an MSN synergistic delivery nanocarrier whose assemblies in cells are detachable can be provided; the nanocarrier is used for the drug delivery of subcellular targeting; the carrier is in a core-shell-hook structure, and adopts MSN as a nuclear material to carry PTX; polymerized polyphenol (EGCg) can be taken as a shell material to package the drugs in MSN (MSN@EGCg) and provide modification sites for a hook; and aptamer AS1411 linked double-stranded DNA (dsDNA-Apt) can be taken as the hook to combine nucleolin and carry Dox. The nanocarrier can respectively deliver the Dox and PTX to nucleuses and cytoplasm, so that intracellular targeting ability of drug delivery can be enhanced; and thus, the system can be applied to the development of antitumor drugs, and has considerable prospects.

Improved G-rich oligonucleotide (GRO) aptamers specific to nucleolin, a method of preparing the aptamers, and a use of the aptamers for diagnosing and / or treating a nucleolin-associated disease, are provided.

The present disclosure provides anti-nucleolin antibodies, methods of producing anti-nucleolin antibodies, and cells producing anti-nucleolin antibodies. Also provided are methods of using anti-nucleolin antibodies in treating malignant and non-malignant diseases.

The invention discloses a preparation method and application of a dual-targeting DNA nano drug-loaded complex. DNA single chains S1, S2, S4, S5, S7 and S8, a nucleic acid aptamer 1, a natural nucleic acid aptamer AS1411 and chemically modified nucleic acid four ligands AS1411-1, AS1411-2 and AS1411-3 are mixed in a TM buffer solution, the mixture is placed in a PCR instrument to be constructed, and a DNA tetrahedral Aptamer 1-AS1411, a DNA tetrahedral Aptamer 1-AS1411-1, a DNA tetrahedral Aptamer 1-AS1411-2 and a DNA tetrahedral Aptamer 1-AS1411-3 are obtained through construction respectively. According to the preparation method and application of the dual-targeting DNA nano drug-loaded complex, four dual-targeting DNA nano drug-loading systems based on CD44 and nucleolin nucleic acid aptamers are constructed, and compared with a single-targeting drug-loading complex and a negative control group, four dual-targeting drug-loaded complexes have stronger nuclease degradation resistance, capability of targeting melanoma A375 cells, capability of inhibiting proliferation of the A375 cells and capability of inducing the A375 cells to generate G1 phase retardation.

The invention relates to a nano probe used for nucleolin cross-linking to induce the tumor cell apoptosis, and a preparation method and application of the nano probe, and belongs to the technical field of biology. The nano probe uses ethylene glycol chitosan as a polymer backbone, the polymer backbone is grafted with cholesterol and an A chain, the 5'end of the A chain is modified with a carboxylgroup, the 3'end of the A chain is modified with a dye Cy3, the A chain contains a nucleic acid adapter AS1411 gene sequence, and the A chain partially hybridizes with a B chain modified with BHQ2 atthe 5'end. The nano probe can selectively kill tumor cells with the overexpression of nucleolin, but has relatively little effects on normal cells, is expected to become a method for the treatment ofmalignant tumors, and provides a new alternative receptor for the idea of receptor cross-linking to induce apoptosis. The nano probe is simple in synthesis, separation and purification, and is suitable for expanded production.

A method of inducing cell death in a glioblastoma multiforme cancer cell is provided, the method comprising administering to the cell a combination of therapeutic agents comprising: saposin C and dioleoylphosphatidylserine (SapC-DOPS), and nucleolin aptamer AS1411, wherein cell death of the cancer cell is induced. Also provided are methods of treating glioblastoma multiforme, methods of inhibiting growth of a glioblastoma multiforme tumor, kits, and pharmaceutical compositions comprising SapC-DOPS and