87 results about "Tumor selectivity" patented technology

Promoters that include a tissue-selective promoter sequence and a second promoter sequence operatively coupled to the tissue-selective promoter sequence, wherein the second promoter sequence includes a minimal viral promoter sequence, are disclosed. Nucleic acids and compositions that include these promoter sequences are also disclosed. Also disclosed are methods of improving the function of a tissue-selective promoter, involving operatively coupling a tissue-selective promoter sequence with a second promoter sequence that includes a minimal viral promoter sequence. Also disclosed are methods of delivering a gene into a cell, methods of treating a subject with a hyperproliferative disease, and methods of imaging a cell that involve use of the novel promoter sequences set forth herein.

The invention belongs to a liposome, in particular relates to a compound liposome preparation with high targeting property of tumor tissues and efficient penetrability of tumor cells. The invention is characterized in that hyaluronic acid or sodium hyaluronate, tumor cell selective penetrating peptides and a liposome are used for together constructing a compound liposome. The compound liposome is characterized by utilizing the dual-tumor cell targeting property of the hyaluronic acid and tumor cell selective penetrating peptides to effectively solve the problem that because a conventional liposome and traditional cell penetrating peptides have no selectivity on normal cells and tumor cells, the toxicity is increased when the drug effect is increased in the therapeutic process, thereby fully meeting the clinical requirements of high efficiency and low toxicity when anti-tumor drugs are prepared into preparations for treating diseases.

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 present invention provides methods and compositions for conferring tumor selective cell death on cancer cells expressing specific target precursor messenger RNA molecules (cancer cell selective target pre-mRNAs). The compositions of the invention include conditionally replicative adenoviruses that have been genetically engineered to express one or more pre-trans-splicing molecules (PTMs) designed to interact with one or more cancer cell target pre-mRNA and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecules (chimeric RNA) capable of encoding adenovirus specific protein(s). Adenovirus specific proteins include those proteins complementing an essential activity necessary for replication of a defective adenovirus. The methods and compositions of the invention may be used to target a lytic adenovirus infection to cancer cells thereby providing a method for selective destruction of cancer cells. In addition, the adenoviruses of the invention may be engineered to encode PTMs designed to interact with target pre-mRNAs encoded by infectious agents within a cell, thereby targeting selective destruction of cells infected with such agents.

The present disclosure provides methods and compositions for enhanced delivery of siRNA or miRNA, into the interior of multilayered tissues, and into the cytoplasm or nucleus of cells of a tissue. Such methods and compositions yield tumor-selective and intracellular delivery of RNAi agents and allow for RNAi-mediated activity such as knock-down of the target genes and associated products. The current disclosure further provides methods and compositions for improving the intracellular bioavailability of nucleotide agents.

Chrome compounds have been discovered which demonstrate impressive cytotoxicity as well as a remarkable ability to inhibit tubulin polymerization. Such compounds as well as related derivatives are excellent clinical candidates for the treatment of cancer in humans. In addition, certain of these ligands, as pro-drugs, may well prove to be tumor selective vascular targeting chemotherapeutic agents or to have vascular targeting activity resulting in the selective prevention and / or destruction of nonmalignant proliferating vasculature.

The present invention provides methods and compositions for conferring tumor selective cell death on cancer cells expressing specific target precursor messenger RNA molecules (cancer cell selective target pre-mRNAs). The compositions of the invention include conditionally replicative adenoviruses that have been genetically engineered to express one or more pre-trans-splicing molecules (PTMs) designed to interact with one or more cancer cell target pre-mRNA and mediate a trans-splicing reaction resulting in the generation of novel chimeric RNA molecules (chimeric RNA) capable of encoding adenovirus specific protein(s). Adenovirus specific proteins include those proteins complementing an essential activity necessary for replication of a defective adenovirus. The methods and compositions of the invention may be used to target a lytic adenovirus infection to cancer cells thereby providing a method for selective destruction of cancer cells. In addition, the adenoviruses of the invention may be engineered to encode PTMs designed to interact with target pre-mRNAs encoded by infectious agents within a cell, thereby targeting selective destruction of cells infected with such agents.

Trimethoxyphenyl substituted indole ligands have been discovered which demonstrate impressive cytotoxicity as well as a remarkable ability to inhibit tubulin polymerization. Such compounds as well as related derivatives are excellent clinical candidates for the treatment of cancer in humans. In addition, certain of these ligands, as pro-drugs, may well prove to be tumor selective vascular targeting chemotherapeutic agents or to have vascular targeting activity resulting in the selective prevention and / or destruction of nonmalignant proliferating vasculature.

Analogs of combretastatin have been discovered which demonstrate impressive cytotoxicity as well as a remarkable ability to inhibit tubulin polymerization. Such compounds are excellent clinical candidates for the treatment of cancer in humans. In addition, certain of these ligands, as pro-drugs, may well prove to be tumor selective vascular targeting chemotherapeutic agents or to have vascular targeting activity resulting in the selective prevention and / or destruction of nonmalignant proliferating vasculature.

The invention discloses a TK (Thymidine Kinase) gene removed recombinant VTT (Tian Tan strain) oncolytic VACA (Vaccinia Virus). A VTT oncolytic VACA is subjected to recombination transformation, a TKgene is removed, and an EGFP (Enhanced Green Fluorescent Protein) gene and a Luciferase gene are expressed. The invention further discloses a preparation method of the TK gene removed recombinant VTToncolytic VACA, which comprises the steps of: recombining a wild type VTT virus and a targeting plasmid aiming at the TK gene of the VTT virus in cells to obtain virus suspension; screening and purifying the virus suspension to obtain the attenuated VTT oncolytic VACA. According to the TK gene removed recombinant VTT oncolytic VACA, which is disclosed by the invention, the TK gene is used as an attenuation target, the EGFP gene and the Luciferase gene are expressed, virus virulence is reduced, and tumor selectivity of the virus is improved; the TK gene removed recombinant VTT oncolytic VACA has a function of monitoring distribution of virus particles in a body, provides a novel antitumor drug for the clinic, can be used for researching and developing a live vaccine and is applicable to various tumors such as the lung cancer, the liver cancer, the melanoma and the like.

The present invention relates to pharmaceutical compositions containing tumor-selective targeted inhibitor glycoconjugates. These bioconjugates are ALK5 inhibitors covalently bound to biocompatible carrier molecules which selectively target and specifically bind to Muc4 that is overexpressed on a variety of tumor cell types. The ALK5 inhibitors are conjugated to tumor targetable glycans through a covalent linker. Preferably the acid-labile linker is designed to be stable in plasma and releases pharmacologically active inhibitors through acid-catalyzed hydrolysis in the acidic environment of the target tumor where the inhibitor activity is restored. Because the glycoconjugates are stable at physiological pH and in plasma, they advantageously reduce undesirable systemic ALK5 inhibitor activity; however, the preferable glycoconjugates are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor.

The present invention relates to a new class of cationic linear polyphosphazenes bearing as side groups a hydrophilic poly(ethylene glycol) and a spacer group selected from the group consisting of lysine, oligopeptides containing lysine, amino-ethanol, amino-propanol, amino-butanol, amino-pentanol and amino-hexanol, and the polyphosphazene-drug conjugates comprising hydrophobic anticancer drugs by covalent bonding and the preparation methods thereof. The present polyphosphazene-drug conjugates exhibit outstanding tumor selectivity and low toxicity.

Anticancer agents which contain as the active ingredient, a heme oxygenase inhibitory metalloporphyrin derivatives which are conjugated with amphipathic or water-soluble polymers (in particular, Zn-protoporphyrin (ZnPP) conjugated with polyethylene glycol). Because of being conjugated to amphipathic or water-soluble polymers, such as polyethylene glycol, the active ingredient can be administered by intravenous injection and can exert a remarkable anticancer effect owing to tumor selective delivery.

The present invention relates to a novel chlorin e6-folic acid conjugate, a preparation method thereof, and a pharmaceutical composition for the treatment of cancer comprising the same, and more particularly, to a novel compound prepared by linking chlorin e6 to folic acid, which effectively produces singlet oxygen in various media and has much better tumor selectivity than the known porphyrin-based photosensitizers, thereby being used effectively in photodynamic therapy for malignant tumors, a preparation method thereof, and a pharmaceutical composition for photodynamic treatment of solid tumors comprising the compound.

The present disclosure provides methods and compositions for enhanced delivery of siRNA or miRNA, into the interior of multilayered tissues, and into the cytoplasm or nucleus of cells of a tissue. Such methods and compositions yield tumor-selective and intracellular delivery of RNAi agents and allow for RNAi-mediated activity such as knock-down of the target genes and associated products. The current disclosure further provides methods and compositions for improving the intracellular bioavailability of nucleotide agents.

Belonging to the genetic engineering field in medicine, the invention discloses a construction scheme for artificially modified human adenovirus type 5 (Ad5), and specific application of a tumor-selective replicative adenovirus construct in tumor treatment. With the techniques of PCR (polymerase chain reaction) amplifying fixed point deletion, enzyme cutting, connection, cloning, homologous recombination, transfection, single cloning purification of adenovirus and the like, a recombinant adenovirus construct can be acquired. Acquisition of the construct is characterized in that: 27 bases are deleted in 2(CR2) region of E1A conserved sequence of Ad5 genome; 28530-29360nt in 6.7k / gp19k gene in E3 region are deleted, and meanwhile a fragment of full-length cDNA(1131bp) of HSV-TK (herpes simplex virus thymidine kinase) is inserted into the deletion region. The construct of the invention is a novel oncolytic adenovirus carrier with high tumor-selective replication capability. With the suicide gene of HSV-TK and dissolubility of tumor cells by oncolytic viruses, the dual killing effects have unique utility value in tumor biotherapy.

Compositions and methods for cancer therapy are disclosed. More particularly, the present disclosure relates to tumor-selective chitosan protected gold nanoraspberries for photothermal cancer therapy.

The invention relates to an 18F-fluorine labeling pentapeptide complex and a synthetic method thereof. The 18F-fluorine labeling pentapeptide complex has a chemical structural formula as shown in a formula 1, and a positron emission computed tomography tracer agent which has the advantages of good hydrophilicity and targeting on tumors can be prepared by utilizing the 18F-fluorine labeling pentapeptide complex. The method for synthesizing the 18F-fluorine labeling pentapeptide complex comprises the following steps of: (1) reacting a cyclic polyamine polycarboxylic compound with a pentapeptide compound, and connecting through a covalent bond to form a ligand; (2) reacting the ligand obtained from the step (1) with 18F-potassium fluoride and aluminum chloride to form the 18F-fluorine labeling pentapeptide complex. The 18F-fluorine labeling pentapeptide complex disclosed by the invention can be selectivity ingested and enriched by the tumors and achieves higher concentration in the tumors, thereby realizing the targeted imaging of the tumors and enhancing the contrast ratio and definition of the imaging.

The invention relates to the field of medicine, in particular to a bionic nano medicament and a preparation method and application thereof. The nano medicament comprises an inner core and a shell withwhich the inner core is coated; the inner core comprises a first component, a second component and a carrier the side chain of which contains sensitive bonds; the shell comprises a cancer cell membrane. The carrier of the sensitive bonds stays in a weak acid environment and is rapidly swelled, an anti-cancer medicament TMZ and the second component are efficiently released, and the cancer cell membrane serving as the shell is made into the nano medicament, wherein the cancer cell membrane has certain self-recognition and high tumor selectivity for targeting in-vivo homologous homing tumors, and the in-vivo circulation time of the nano medicament can be greatly prolonged. The cancer cell membrane serving as the shell and the carrier of the sensitive bonds efficiently release the anti-cancermedicament TMZ and the second component, and finally tumor cells are killed, so that the purpose of targeted synergistic treatment of human brain gliomas is achieved.

The invention provides a human primary tumor cell separation and culture kit, consisting of a packing box, a cell culture plate with 6 pores, cleaning solution, trypsinization solution, collagenase-hyaluronidase digestive juice, a cell separating medium, selective tumor culture solution and an operating instruction, wherein sterile RPMI (Roswell Park Memorial Institute) 1640 cell culture solutioncontaining 400U / mL of penicillin and 400 mu g / mL of streptomycin serves as the cleaning solution. The human primary tumor cell separation and culture kit solves the problems that the conventional primary tumor cell culture process is complicated, the purity of obtained tumor cells are not high, and the tumor cells are easy to be contaminated by cells. According to the invention, the design is reasonable, the opportunity of germ contamination is less in the process of separation and culture of primary tumor cells in vitro, and only a few of centrifugal tubes and other common consumable items are needed, so that the kit is simple and convenient to use, the purity of the cultured tumor cells is higher, and the effect is good.

Disclosed is a recombinant human adenovirus type 5 adenovirus construct, in which a 920-946 nt sequence of ADV5 genome and a 28532-29360 nt sequence of the E3 region are deleted while a foreign cDNA fragment is reversely inserted into the deleted E3 region. A method for preparing the recombinant ADV5 construct is also provided. The construct provided herein presents a tumor-specific replication, tumor-specific expression of the inserted anti-gene and tumor-specific bystander effects, and is suitable for use in tumor therapy.

Anticancer agents which contain as the active ingredient, a heme oxygenase inhibitory metalloporphyrin derivatives which are conjugated with amphipathic or water-soluble polymers (in particular, Zn-protoporphyrin (ZnPP) conjugated with polyethylene glycol). Because of being conjugated to amphipathic or water-soluble polymers, such as polyethylene glycol, the active ingredient can be administered by intravenous injection and can exert a remarkable anticancer effect owing to tumor selective delivery.

Trimethoxyphenyl substituted indole ligands have been discovered which demonstrate impressive cytotoxicity as well as a remarkable ability to inhibit tubulin assembly. Such compounds as well as related derivatives are excellent clinical candidates for the treatment of cancer in humans. In addition, certain of these ligands, as pro-drugs, may well prove to be tumor selective vascular targeting chemotherapeutic agents or to have vascular targeting activity resulting in the selective prevention and / or destruction of nonmalignant proliferating vasculature.

The invention belongs to the chemical field of natural medicine and discloses a blood flower milkweed milk extract rich in cardiac glycosides as well as a preparation method and an application of the extract. The preparation method of the extract comprises the following steps: (1) diluting the milk of the blood flower milkweed by use of water to obtain a diluent; adding an organic solvent to the diluent for extracting, and collecting the organic layer obtained after extraction; next, adding the organic solvent to the left water layer for extracting, collecting the organic layer again, and circularly extracting for 2-4 times, and then abandoning the water layer, and blending the organic the organic layers to obtain the cardiac glycoside extract of the blood flower milkweed milk; (2) performing reduced pressure concentration on the blood flower milkweed milk until a constant weight, thereby obtaining the blood flower milkweed milk extract rich in cardiac glycosides. The blood flower milkweed milk extract rich in cardiac glycosides has excellent anti-tumor activity and low toxicity to normal cells; the extract contains a plurality of types of cardiac glycosides rich in content. The preparation method of the blood flower milkweed milk extract rich in cardiac glycosides is simple, low in cost, high in extraction rate, and high in anti-tumor selectivity.

The present invention relates to pharmaceutical compositions containing tumor-selective targeted inhibitor glycoconjugates. These bioconjugates are ALK5 inhibitors covalently bound to biocompatible carrier molecules which selectively target and specifically bind to Muc4 that is overexpressed on a variety of tumor cell types. The ALK5 inhibitors are conjugated to tumor targetable glycans through a covalent linker. Preferably the acid-labile linker is designed to be stable in plasma and releases pharmacologically active inhibitors through acid-catalyzed hydrolysis in the acidic environment of the target tumor where the inhibitor activity is restored. Because the glycoconjugates are stable at physiological pH and in plasma, they advantageously reduce undesirable systemic ALK5 inhibitor activity; however, the preferable glycoconjugates are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor.

The invention discloses a construction scheme of artificially transforming human type 5 adenovirus (Ad5), and a specific application of a novel oncolytic adenovirus construct obtained by the scheme in tumor treatment, and belongs to the technical field of medical genetic engineering. A recombinant adenovirus construct obtained by PCR amplification site-directed deletion, enzyme digestion, ligation, cloning, homologous recombination, transfection, adenovirus monoclonal purification, etc., its technical characteristics are: Ad5 genome E1A conserved sequence 2 27 bases were deleted in the (CR2) region; 29477-29714nt of the ADP gene in the E3 region was deleted; and the full-length coding sequence (1131bp) of the HSV-TK gene was inserted in the deleted region. This construct is a new type of oncolytic adenoviral vector with higher tumor selective replication ability, which utilizes the suicide gene function of HSV-TK and the double killing effect of oncolytic virus to dissolve tumor cells, and has great potential in the biological treatment of tumors. Unique practical value.

The invention relates to a sulfonium salt stable targeting HDAC polypeptide drug conjugate and application thereof, a sulfonium salt stable apoptosis-promoting polypeptide is coupled with an HDAC inhibitor to form a stable polypeptide HDAC inhibitor with tumor selective toxicity, the nonspecific toxicity of apoptosis polypeptide chemically stabilized by sulfonium salt is remarkably reduced, the stability of protease is higher, and the tumor selective toxicity of the apoptosis polypeptide is remarkably reduced. When a polypeptide drug conjugate is formed by coupling with an HDAC inhibitor, the polypeptide drug can significantly improve the selective toxicity to tumor cells, and has weak toxicity to normal cells. Cell proliferation, cell apoptosis and cell cycle arrest experiments prove that the polypeptide can effectively inhibit proliferation of malignant liver cancer, has relatively good biological safety and has a potential anti-tumor clinical application prospect.

The invention relates to an oncolytic adenovirus for the treatment of cancer, containing a human DNA sequence isolating a promoter conferring selective expression on an adenoviral gene. Said adenovirus can also contain a sequence that optimises the protein translation of an adenoviral gene regulated by a promoter conferring tumour selectivity. The invention is suitable for use in the treatment of cancer.

The invention discloses a platinum-based compound based on nucleolar stress, wherein the platinum-based compound is a platinum-based antitumor compound formed by carrying out a nitrile-secondary amineClick reaction on cis-monochloro mononitrile diamino platinum and a primary amine-containing RNA polymerase I inhibitor. According to the present invention, the platinum-based antitumor compound hasgood RNA polymerase I inhibitory activity and good tumor selectivity, such that the platinum-based compound has antitumor activity suprior to classical platinum-based drugs, and can reduce toxic-sideeffects and overcome the drug resistance of clinical platinum-based drugs.