27 results about "Nucleolin" patented technology

The invention discloses a BRIX1 inhibitor and application of the BRIX1 inhibitor in tumor resistance, and particularly discloses a nucleoprotein BRIX1 which is a key regulatory factor of a steady state between ribosome biogenesis and p53 activation. Research results show that inhibition of BRIX1 can induce nucleolus stress to activate p53, so that growth of tumors is inhibited. Besides, the engineered exosome is constructed, the surface of the engineered exosome is decorated with iRGD, and the engineered exosome is loaded with siRNA with BRIX1 specificity and is used for treating cancers.

The invention discloses a preparation method and application of programmable DNA hydrogel for inhibiting breast cancer tumor activity. The DNA hydrogel is composed of an RCA long chain AL containing a multivalent AS411 aptamer sequence and an RCA long chain CL hybridized with a cholesterol single chain ss-chol. Through reasonable DNA programming sequence design, a three-dimensional DNA structure can be formed on the surface of the cell. The DNA hydrogel specifically targets cancer cells with high expression of nucleolin receptors through the synergistic effect of multivalent AS1411 and chol, and is weak in targeting to normal cells with low expression of nucleolin, so that toxic and side effects on the normal cells are effectively avoided. The DNA hydrogel has excellent programmability, hydrogel with high, medium and low pore densities can be simply prepared through flexible DNA sequence design, and the breast cancer resistance activity of the DNA hydrogel is in positive correlation with the pore density of the DNA hydrogel. In animal in-vivo experiments, the DNA hydrogel under three-dimensional and high pore density significantly inhibits breast cancer activity, and a new strategy is provided for tumor treatment.

Disclosed in the present invention are a BRIX1 inhibitor and use thereof in resisting tumors. Specifically, disclosed in the present invention is that nucleolin BRIX1 is a key regulator of the homeostasis between ribosome biogenesis and p53 activation. The research results of the present invention show that the inhibition of BRIX1 can induce nucleolar stress, leading to activation of p53, thereby inhibiting tumor growth. In addition, the present invention constructs an engineered exosome whose surface is decorated with iRGD and which is loaded with BRIX1-specific siRNA and used for cancer therapy.

The invention discloses a nucleolin aptamer modified carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system as well as a preparation method and application thereof, and relates to the field of tumor treatment. The nucleolin aptamer AS1411 is coupled with glycolysis regulation nano-particles through covalent bonds, and the carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system comprises a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system and a carboxymethyl chitosan-based glycolysis regulation nano-drug delivery system, the glycolysis regulation nano-particles take carboxymethyl chitosan as a carrier skeleton, the carrier skeleton is loaded with a lonidamine derivative through grafting modification, and the nano drug delivery system can synchronously entrap paclitaxel. According to the invention, a synergistic treatment system integrating active targeting, metabolic regulation and chemotherapy is constructed, and by virtue of a multi-mechanism synergistic effect, an antitumor drug for inhibiting tumor cell activity, glycolysis or tumor metabolism reprogramming is prepared; the huge potentials of overcoming the drug resistance bottleneck of traditional chemotherapy, enhancing the curative effect and reducing the toxic and side effects are shown.

The application provides application of nucleolin as a drug target in preparation of a double-targeted treatment drug for colorectal cancer, and application of nucleolin as a double-targeted drug target in preparation of a drug for double-targeted killing of colorectal cancer tumor cells and tumor-related fibroblasts, the drug for double-targeted killing of colorectal cancer tumor cells and tumor-related fibroblasts, a pharmaceutical composition containing the drug and application thereof. The application uses nucleolin as a common drug target of colorectal cancer tumor cells and tumor-related fibroblasts, applies a double-targeted killing drug with nucleolin as a target, simultaneously kills colorectal cancer tumor cells and tumor-related fibroblasts, removes tumor cells while destroying tumor-related fibroblast-mediated tumor supporting microenvironment, and synergistically enhances the overall treatment effect of colorectal cancer.

It provides a complex for target protein degradation. [Solution] The present invention relates to a novel compound-peptide nucleic acid-aptamer complex for targeted protein degradation and its applications. The complex is manufactured by binding a novel compound to a peptide nucleic acid and introducing an aptamer that can bind complementaryly to the peptide nucleic acid. It has been confirmed to have the effect of targeting and degrading intracellular target proteins such as Tau, nucleolin, and eIF4E, and can be usefully utilized in related industries.

The present invention relates to a novel peptide that specifically binds to nucleolin, and more specifically, to a peptide expressed by a specific amino acid sequence, a conjugate comprising the peptide and an anticancer drug, a fusion peptide comprising the peptide and a cell-penetrating peptide, a composition comprising the peptide for diagnosing cancer, and a composition comprising the peptide or the conjugate for preventing or treating cancer. In the present invention, the peptide ligand AGM peptide and its mutants, screened using the MAP synthesis method and the OBOC combination method, have been shown to specifically bind to cancer cells, and their conjugates with anticancer drugs inhibit cancer growth (in vitro and in vivo). Therefore, the AGM peptide targeting nucleolin can be effectively used for diagnosis and targeted drug delivery in cancer treatment.

The application belongs to the technical field of molecular detection, and particularly relates to a method for detecting NCL conformation and G4 complex thereof based on a solid nanopore. The method is as follows: a solid nanopore is used, bias is applied on both sides of the nanopore, translocation signals of a sample to be tested through the nanopore are tested under the condition of the applied bias, and nucleolin in the sample to be tested is qualitatively and / or quantitatively analyzed through the translocation signals. By analyzing the blocking current amplitude and translocation time of NCL and G4 complex thereof entering the nanopore channel under bias, information such as the size and electrification of NCL and G4 complex thereof can be obtained. The application can detect NCL of different concentrations, greatly reduce the test cost, and at the same time, trace detection of NCL can be realized with high sensitivity and rapidness. The application provides a new research idea for targeted treatment of diseases such as cancer through detection of NCL and NCL-G4 complex.

Disclosed are a protein degrader targeting O-GlcNAc Transferase (OGT), and a preparation method therefor and a use thereof. The inventors of the present invention have creatively discovered that a compound recruits MDM2 by means of its interaction with nucleolin (NCL), and through further experiments have found that it can serve as a novel recruiting element for MDM2, which can be used in the preparation of targeted protein degraders and other applications. Using the above findings, the inventors have prepared a novel protein degrader compound targeting OGT, and have found through experimentation that the prepared targeted protein degrader can effectively induce the degradation of OGT, for use in the treatment of diseases mediated by OGT or associated with O-GlcNAc glycosylation (such as neurodegenerative diseases, obesity, tumors, diabetes and complications thereof, cardiovascular diseases, etc.), and will have very promising application prospects in the fields of medicine and health management.

The present invention belongs to the field of protein targeted degradation chimera preparation and biomedicine technology, and specifically relates to a conditional protein targeted degradation chimera based on nucleic acid aptamers, and its preparation method and application. The present invention uses nucleic acid aptamers that specifically target nucleolin as ligands to develop a series of chimera degraders for nucleolin. Further, by introducing a photosensitive nucleic acid aptamer complementary chain, a chimera that conditionally degrades nucleolin is developed, thereby achieving spatiotemporal controllable degradation of nucleolin. The protein targeted degradation chimera prepared by the present invention has good degradation efficiency and anti-tumor cell effect; at the same time, the use of nucleotides as connecting molecules greatly simplifies the difficulty of synthesizing E3 ligands; in addition, regulating the chimera activity by regulating the conformation of nucleic acid aptamers provides a new method for specifically degrading pathogenic proteins in diseased tissues, greatly reducing the toxic and side effects of chimeras on normal tissues, and has good practical application value.

The present invention discloses a series of novel redox-responsive nucleolin aptamer-paclitaxel conjugates as shown in formula I, a preparation method thereof and an application thereof: #imgabs0#R is -(CH2) m1 S(CH2) n1 ‑,‑(CH2) m2 SS(CH2) n2 ‑、‑(CH2) m3 SC(CH3)2S(CH2) n3 ‑, m1, n1, m2, n2, m3, n3 are 0 or positive integers. The conjugate is designed to respond to the redox heterogeneity of triple-negative breast cancer, has good water solubility and tumor specificity, and exhibits redox dual responsiveness, rapid release of PTX, and the highest anti-triple-negative breast cancer ability.

The present invention discloses the application of nucleolin in blocking porcine reproductive and respiratory syndrome virus infection, and belongs to the field of biotechnology. The present invention discovers a new PRRSV cell target protein - Nucleolin protein (NCL), and the specific siRNA for NCL and the single-stranded oligonucleotide AS1411 with specific affinity for NCL can significantly inhibit PRRSV infection, and the combined application of the two can significantly improve the ability to resist PRRSV infection. The specific siRNA of NCL and AS1411 can be developed into drugs for preventing and treating PRRSV infection, thereby providing a new idea for PRRSV research and prevention, expanding the scope of research, and having extremely important significance for actual production.

The present invention relates to an antiviral use of a novel peptide binding specifically to nucleolin and, more specifically, to: an antiviral composition comprising a peptide represented by a specific amino acid sequence; an antiviral composition comprising a fusion peptide in which the peptide and a cell-penetrating peptide are coupled to each other; a composition comprising the aforementioned compositions for preventing or treating a viral infection; and a health functional food composition for prevention or alleviation of a viral infection. In the present invention, a AGM peptide ligand and mutants thereof were found to inhibit viral proliferation and replication (in vitro and in vivo), as screened by an MAP synthesis method and an OBOC combination method. Therefore, NCL-targeting AGM can find advantageous applications in antiviral uses.

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 invention discloses a DNA (Deoxyribose Nucleic Acid) aptamer for targeting nucleolin and application of the DNA aptamer, belongs to the technical field of oligonucleotides, and particularly relates to the DNA aptamer for targeting nucleolin. The DNA nucleic acid aptamer is obtained by reacting AS1411 of which the 5'end is modified by amino and a triptolide derivative; the triptolide derivative is obtained by modifying triptolide with a vinyl carboxylic acid derivative; the vinyl carboxylic acid derivative is prepared by the following preparation steps: under the action of a catalyst, allyl succinic anhydride firstly reacts with 4-(chloromethyl) benzyl alcohol, and then reacts with sodium bicarbonate to obtain the vinyl carboxylic acid derivative. The DNA aptamer for targeting nucleolin disclosed by the invention not only can be efficiently combined with nucleolin, but also has good effects of inhibiting tumor cell proliferation and inhibiting tumor growth.

Provided herein are compositions including aptamers capable of binding to and / or inhibiting the activity of nucleolin. Methods of treating cancer in a subject by administering such compositions are also provided.

The invention belongs to the technical field of nucleic acid aptamers, and particularly relates to a nucleic acid aptamer-loaded ruthenium (II) complex nano net as well as a preparation method and application thereof. The aptamer-loaded ruthenium (II) complex nano net provided by the invention can specifically recognize cancer cells in a targeting manner, and can reduce cytotoxicity. The ruthenium (II) complex is combined with the nucleic acid aptamer, so that the defects that the nucleic acid aptamer is unstable in metabolism and easy to remove by nuclease are overcome, the structural stability and the biological activity of the nucleic acid aptamer loaded ruthenium (II) complex nano net are improved, the compound can specifically recognize nucleolin in tumor cells, G4DNA conformation is formed, and the tumor cells can be specifically recognized. And targeted recognition of tumor cells is realized.

The invention provides a construction method of a mouse heart failure model based on NCL gene myocardial specific knockout induction and application of NCL gene myocardial knockout. According to the method, Nclflox / flox and Myh6-Cre mice of 5-6 weeks old are used, NCL genes in cardiac muscle cells of the mice are specifically knocked out, the mice are continuously fed until the ejection fraction of a left ventricle is smaller than 50%, and the adult mouse heart failure model based on cardiac muscle cell nucleolin specific knockout is obtained. The successful construction of the model provides a key technical support for exploring heart diseases mediated by nucleolin-related pathways in myocardial cells, effectively fills the blank of demands of the research field in the aspect of experimental vectors, and has indispensable important significance for promoting heart disease mechanism research and transforming medical development.

The invention discloses application of a substance aiming at a VDAC1 target spot in preparation of a product and a medicine for preventing and treating diseases caused by RSV, and relates to the technical field of respiratory syncytial virus resistance. A novel RSV cell receptor VDAC1 (voltage-dependent anion channel 1) independent of NCL (nucleolin) is discovered, a novel RSV infected cell receptor is identified, and discovery of the receptor provides a molecular basis for development of novel antiviral drugs and is crucial for development of novel drugs. The substance aiming at the VDAC1 target spot, provided by the invention, has a good application prospect in prevention and treatment of diseases caused by RSV, and the resistance of a subject to RSV infection can be greatly improved.

Provided is use of a monophosphate deoxyribose fluorouracil nucleoside prodrug in the preparation of a drug for preventing and / or treating tumors. The monophosphate deoxyribose fluorouracil nucleoside prodrug is a derivative formed by substituting at least one thymine in nucleolin aptamer AS1411 with fluorouracil. The tumors include at least one of lung cancer, breast cancer, prostate cancer, pancreatic cancer, kidney cancer, cervical cancer, leukemia and lymphoma, melanoma, glioblastoma, neuroblastoma, sarcoma, and gastric cancer. The monophosphate deoxyribose fluorouracil nucleoside prodrug binds to the nucleolin protein and selectively enters tumor cells under the action of the nucleolin protein, and release an antimetabolite to inhibit thymine nucleotide synthase, thereby achieving an anti-tumor effect.

The invention belongs to the technical field of cancer treatment, and discloses an application of an sTREM2-NCL-AKT / eNOS axis in the vascular permeability of ovarian cancer and the formation of malignant ascites. The invention proves that the level of the sTREM2 is increased in ascites of an ovarian cancer patient, discloses the effect of the sTREM2 in promoting vascular permeability and driving ascites formation, and puts forward that the sTREM2 has double values of a prognosis biomarker and a potential treatment target. The discovery lays a foundation for developing accurate treatment for ovarian cancer and malignant ascites. In mechanism, the sTREM2 activates an AKT / eNOS signal channel through interaction with a cell surface nucleolin (NCL) protein, so that the integrity of an endothelial barrier is damaged. Targeting or blocking sTREM2 effectively mitigates vascular leakage and ascites production. According to the discovery, the sTREM2 is determined as a core driving factor of ascites pathogenesis, and the potential of the sTREM2 as an ovarian cancer treatment target is highlighted.

The present invention discloses a bispecific probe-linker complex and a preparation method and use thereof, wherein the bispecific probe-linker complex comprises a linker, a first probe covalently connected to the linker, and a second probe covalently connected to the linker; the first probe can specifically bind to nucleolin protein, and the second probe can specifically bind to CTLA-4. The bispecific probe-linker complex can bind to tumor cells containing nucleolin protein on the surface through the first probe and simultaneously bind to immune cells with CTLA-4 through the second probe, thereby promoting immunotherapy, and has the characteristics of low immunogenicity, easy synthesis, low side toxicity and high efficiency.

The invention discloses a cascade dual-AND logic DNA nano circuit and a preparation method and application thereof, and the cascade dual-AND logic DNA nano circuit comprises a tubular six-helix frame nucleic acid composed of six DNA double helixes and a drug encapsulated in a tubular cavity of the tubular six-helix frame nucleic acid, the tubular six-helix framework nucleic acid is mainly synthesized by DNA single-stranded hybridization with nucleotide sequences shown as SEQ ID NO: 1-20, and the drug is connected with the tubular six-helix framework nucleic acid through a disulfide bond. The cascade dual-AND logic DNA nanocircuit provided by the invention has a cascade dual-AND logic gate, can sequentially respond to three tumor specific signals of acidic pH, nucleolin and glutathione according to a strict space-time sequence, and can realize accurate release of drugs when being applied to drug delivery, thereby minimizing off-target toxicity and remarkably improving the treatment effect of the drugs.

The present invention relates to a novel peptide that specifically binds to nucleolin and, more specifically, to a peptide represented by a specific amino acid sequence, a conjugate comprising the peptide and an anticancer drug, a fusion peptide comprising the peptide and a cell-penetrating peptide, a composition for diagnosing cancer comprising the peptide, and a composition for preventing or treating cancer comprising the peptide or the conjugate. In the present invention, it has been confirmed that a peptide ligand AGM peptide and mutants thereof, as screened using an MAP synthesis method and an OBOC combination method, specifically bind to cancer cells, and a conjugate thereof with an anticancer drug inhibits cancer growth (in vitro and in vivo). Thus, the NCL-targeting AGM peptide can be effectively used for diagnosis and targeted drug delivery in cancer therapy.

Disclosed are compositions and methods for performing nucleic-acid-based assays to determine the presence or absence of a target nucleic acid in a biological sample. The disclosed methods include the use of one or more oligomers that specifically hybridize to a nucleolin nucleic acid to assess the cellularity of the biological sample. Also disclosed are related composition and methods for assessing the cellularity of a biological sample for use in a molecular diagnostic assay.

The invention belongs to the technical field of biological medicine, and particularly discloses application of nucleolus phosphoprotein 1 in esophageal cancer diagnosis products and / or prognosis evaluation products and treatment drugs. Bioinformatics analysis and clinical sample verification prove that the mRNA and protein levels of the nucleophosphoprotein 1 in esophageal cancer tumor tissues are obviously higher than those in normal tissues, and the expression level of the nucleophosphoprotein 1 is positively correlated with T stages and M stages of tumors, so that the nucleophosphoprotein 1 can be used as a marker for prognosis evaluation of esophageal cancer. Further functional experiments prove that the siRNA is used for knocking down the expression of the nucleolus phosphoprotein 1, so that proliferation and migration of esophageal cancer cells can be remarkably inhibited, cell apoptosis is induced, and cell cycle arrest is caused. The technical problems that early diagnosis of esophageal cancer is difficult, and existing molecular markers are insufficient in sensitivity and lack of effective treatment intervention targets are solved.

Disclosed in the present invention are a BRIX1 inhibitor and use thereof in resisting tumors. Specifically, disclosed in the present invention is that nucleolin BRIX1 is a key regulator of the homeostasis between ribosome biogenesis and p53 activation. The research results of the present invention show that the inhibition of BRIX1 can induce nucleolar stress, leading to activation of p53, thereby inhibiting tumor growth. In addition, the present invention constructs an engineered exosome whose surface is decorated with iRGD and which is loaded with BRIX1-specific siRNA and used for cancer therapy.