88results about How to "Improve tumor targeting" patented technology

The invention relates to human pluripotent stem cell exosomes loaded with antitumor drugs and a preparation method and use of the human pluripotent stem cell exosomes. According to the method, the human pluripotent stem cell exosomes are taken as nanoscale carriers of the antitumor drugs, and by performing RGD peptide artificial modification on the surfaces of the exosomes, the exosomes have stronger tumor targeting, thereby constructing a natural drug delivery system easily passing through a blood brain barrier and having the tumor targeting. The human pluripotent stem cell exosomes loaded with the antitumor drugs have both the tumor resistance, immune adjustment, inflammatory resistance and other functions of pluripotent stem cell exosomes and the specific antitumor function of the antitumor drugs; the dual functions of the pluripotent stem cell exosomes and the antitumor drugs can better exert the antitumor effect and greatly reduce the dosage of the antitumor drugs, thereby greatlyreducing the toxic and side effects of the antitumor drugs; by using the nanoscale properties of the exosomes, the exosomes can pass through the blood brain barrier, thereby having unique advantagesfor the treatment of central nervous system tumors; the human pluripotent stem cell exosomes loaded with the drugs are modified by RGD peptides, thereby greatly enhancing tumor targeting of the exosomes.

The invention discloses a preparation method of PAMAM and CRISPR/Cas9 system recombinant plasmid delivering nanoparticles with tumor targeting. Firstly, Apt carboxyl is activated, Apt is reacted withamino on the surface of PAMAM to synthesize an Apt-PAMAM carrier, sgRNA is designed, an EGFR-sgRNA/Cas9 recombiant plasmid is constructed, and the recombiant plasmid and the carrier form an Apt-PAMAM/EGFR-sgRNA/Cas9 nano compound through electrostatic interaction. According to the compound, by means of compound surface-modified Apt active targeting tumor cell surface high expression EpCAM protein,tumor tissue targeting is improved; through a CRISPR/Cas9 gene editing technology, the recombiant plasmid of an EGFR-sgRNA gene is designed to knock out a high-expression EGFR gene in a tumor cell, so that the anti-tumor effect is achieved.

The invention discloses a tumor-targeted delivery carrier based on cell-derived micro-vacuoles, a preparation method and an application. The preparation method comprises the following steps of: (A) preparing a conditioned medium: supplementing fetal bovine serum, antibiotics, DSPE-PEG-Biotin and DSPE-PEG-Folate into a basal medium; (B) using the obtained conditioned medium in cell culture, and collecting cell culture supernatant for subsequent separation; (C) carrying out low-speed centrifugation on the obtained culture supernatant to remove cell debris and apoptotic bodies, then adding SA-IONPs, mixing uniformly, incubating, then separating by a magnet, using PBS for re-suspension, eluting for multiple times to obtain the cell-derived micro-vacuoles with membrane surfaces modified by folic acid and iron oxide nano-particles, and freezing for storage; and (D) loading chemotherapeutic drugs or therapeutic genes into the functionalized micro-vacuoles doubly-modified by an electroporation mode, and carrying out re-suspension after separation with the magnet. The tumor-targeted delivery carrier based on cell-derived micro-vacuoles, the preparation method and the application disclosed by the invention are applicable to specific targeting delivery of multiple chemotherapeutic drugs and therapeutic genes, and have the advantages of enhancing the anti-tumor effect, reducing the systemic toxicity and improving the clinical effect of the current therapeutic selection, so that a new hope is brought for clinical therapy of tumors.

The invention discloses a protein-polymer composite nano-carrier and a preparation method thereof and relates to the field of nano preparations of antitumor medicines. The protein-polymer composite nano-carrier is designed and developed on the basis of the characteristics of a lipoprotein structure of a human body and comprises a polymer core and a hydrophilic protein shell; a targeting ligand can be flexibly modified according to the treatment requirement, so as to construct the protein-polymer composite nano-carrier with active targeting property; the in vivo stability of the medicine is improved; the tumor targeting property is increased. In order to increase the load rate of the protein on the polymer kernel, a cationic additive is added to the formula to prepare a cationic polymer nanoparticle; nano suspension is milk white liquid; spherical particles with relatively uniform distribution can be seen by scanning through a transmission electron microscope. A freeze-drying protective additive is added for freeze-drying the nano suspension to form powder, so that the protein-polymer composite nano-carrier is relatively easy to store and the stability is improved. The protein-polymer composite nano-carrier prepared by the method is uniform in particle size and good in stability; and a fat-soluble antitumor medicine can be effectively encapsulated.

The invention discloses a core-shell type nano-contrast agent. The core-shell type nano-contrast agent comprises gadolinium ions and human serum albumin assembled outside the gadolinium ions and serving as a protecting group. The invention further provides a preparation method of the core-shell type nano-contrast agent. The core-shell type nano-contrast agent disclosed by the invention is combined with a nano-technology, and the human serum albumin is taken as a carrier for wrapping the paramagnetic metal gadolinium ions, thus MRI (magnetic resonance imaging) is realized, and biocompatibility and a tumor targeting property are improved; the prepared core-shell type nano-contrast agent has the advantages of small particle size and low biotoxicity; and the preparation method provided by the invention is simple.

The invention relates to methoxy polyethylene glycol-poly-N-isopropyl acrylamide-metal tetramino phthalocyanine and a preparation method therefor and belongs to the field of photodynamic therapy. Methoxy polyethylene glycol-poly-N-isopropyl acrylamide-metal tetramino phthalocyanine is used for solving the problem that the existing phthalocyanine photosensitizer is poor in water solubility and low in tumor targeting performance and the application in the photodynamic therapy is limited by unstable PI-PI accumulative action. Methoxy polyethylene glycol-poly-N-isopropyl acrylamide-metal tetramino phthalocyanine disclosed by the invention has the skeleton symbol of MPEG-PNIPAM-MTAPc, wherein MPEG means methoxy polyethylene glycol, PNIPAM means poly-N-isopropyl acrylamide, and MTAPc means metal tetramino phthalocyanine. The preparation method disclosed by the invention comprises the steps: firstly, preparing an ATRP (Atom Transfer Radical Polymerization) initiator MPEG-X from MPEG-OH and a halogenated substance; secondly, initiating an NIPAM (N-isopropyl acrylamide) monomer to subject to ATRP by the initiator, so as to obtain a temperature-sensitive diblock copolymer MPEG-PNIPAM-X; then, carrying out terminal group functionalization on the MPEG-PNIPAM-X with MA (Maleic Anhydride), so as to obtain MPEG-PNIPAM-MA-X; and finally, bonding MTAPc to the MPEG-PNIPAM-MA-X, thereby obtaining the MPEG-PNIPAM-MTAPc. The prepared photosensitizer is good in water solubility and high in tumor targeting performance, is not liable to aggregation in aqueous solutions and is a phthalocyanine photosensitizer with development potential.

The invention provides a photosensitizer prodrug compound, and a preparation method and an application thereof. The compound has a structure represented by formula (I). A disulfide bond is introduced at the N end of 5-ALA or its ester derivative, the disulfide bond is a GSH responsive group, the group containing the disulfide bond undergoes self-immolative reaction under the condition of linking urethane to the beta position of the disulfide bond in order to release the connected 5-ALA or its ester derivative, protoporphyrin is generated in an intracellular metabolism manner, and the photosensitizer plays a role in photodynamic diagnosis, so dimerization induced inactivation of the 5-ALA is avoided, and the drug stability is increased; and the overexpression of the GSH in various tumor cells and the response of the prodrug compound to the GSH enhance the tumor targeting property of the drug. The invention also provides the application of the photosensitizer prodrug compound in the preparation of the drug for photodynamic diagnosis and treatment.

The invention provides a biological membrane-wrapped multi-mode tumor contrast agent as well as a preparation method and application thereof. The biological membrane-wrapped multi-mode tumor contrastagent comprises a biological membrane, a ferritin nanometer cage (M-HFn) of superparamagnetic ferroferric oxide and a fluorescent dye, wherein the ferritin nanometer cage (M-HFn) of the superparamagnetic ferroferric oxide and the fluorescent dye are wrapped with the biological membrane and are connected with each other to form a fluorescent dye-M-HFn compound, a bionic nanometer biological membrane vector delivery system in vivo is constructed, in vivo long circulation can be realized, targeting to a tumor is strengthened, non-specific accumulation is reduced, damages on normal tissues are reduced, and the contrast effect is strengthened at the same time. The invention also provides a preparation method of the biological membrane-wrapped multi-mode tumor contrast agent, and the preparationmethod has important application prospect and study value in the field of clinic oncology early diagnosis and treatment and the like.

The invention relates to the technical field of preparing a contrast agent by utilizing a hyperbranched polymer. A preparing method of the hyperbranched polymer includes reacting a lysine salt and caustic alkali in a mole ratio of 100:80-90 at 140-160 DEG C for 40-50 h in a protective atmosphere; mixing a hyperbranched polylysine skeleton and diethylenetriaminepentaacetic acid according to a mass ratio of at least 1:5 in water; reacting the mixture at room temperature for 6-8 h; mixing the first hyperbranched polylysine molecule and a gadolinium compound in water; reacting the mixture at 37-42 DEG C for 6-12 h, with the mass ratio of the first hyperbranched polylysine molecule to the gadolinium compound being 1:1-1:2; and mixing and reacting the second hyperbranched polylysine molecule and folic acid in a carbonate the pH value of which is 8-10 for 5-12 h. The hyperbranched polylysine contrast agent has good biocompatibility, low toxicity and a high relaxation rate and can be metabolized in vivo.

The invention discloses a taxol liposome preparation with an active tumor targeting function. The preparation is prepared from taxol, egg yolk lecithin, cholesterol, phosphatidylethanolamine pegol, tbFGF-PEG-DSPE (truncated basic fibroblast growth factor-polyethylene glycol-distearoyl phosphatidylethanolamine) and injection water. According to the preparation, tbFGF capable of being specifically combined with tumor cells and tumor angiogenic blood vessels and maleinimide-polyethylene glycol-phospholipid (DSPE-PEG-MAL) are chemically coupled, thus preparing the tbFGF-PEG-DSPE, and a liposome is prepared from a coupling product and wraps the taxol, thus building a liposome dosage form with long circulation and active tumor targeting functions; therefore, the active tumor targeting and tumor resisting effects are enhanced.

The invention belongs to the technical field of pharmaceutical chemicals and discloses segmented copolymer - docetaxel combination, a preparation thereof and a preparation method thereof. The combination is combined by bonding polyoxyethylene - polypropylene oxide - polyoxyethylene (PEO- b - PPO - b - PEO with a product name as Pluronics (BASF company)) triblock copolymer and docetaxel through ester bond, and the Pluronics - docetaxel combination is obtained. By utilizing amphipathy of the combination and adopting physical methods to prepare micelle aqueous solution, a freeze-dried preparation can also be prepared. Nanomicelle is capable of gathering at tumor parts through 'enhanced permeation and retention effects (EPR effects)', and tumor targeting of docetaxel is enhanced. Besides, an active targeting factor is connected on Pluronics polymer so as to have the function of active targeting. The segmented copolymer - docetaxel combination overcomes the defects that existing docetaxel injection is poor in water-solubility and severe in allergic reaction and the like.

The invention relates to a near-infrared nano photosensitizer as well as a preparation method and application thereof, and relates to the technical field of photosensitizers. According to the near-infrared nano photosensitizer disclosed by the invention, the absorption and emission spectrum of the near-infrared nano photosensitizer is close to a near-infrared light region by performing conjugate extension modification on a BODIPY parent nucleus; introducing a polyfluoroalkane group and a polyethylene glycol group into the BODIPY structure to obtain the amphiphilic photosensitizer; the nano photosensitive micelle with an ultralow CMC (Carboxymethyl Cellulose) value is finally constructed by utilizing the strong fluorine-fluorine action between the polyfluoroalkane groups and the hydrophilic action of the polyethylene glycol groups; j-aggregation of the BODIPY is induced by utilizing a fluorine-fluorine effect, so that the maximum absorption peak of the BODIPY is red-shifted to a near-infrared region, and deep phototherapy of tumors is facilitated.

The invention belongs to the technical field of medicines, and provides a sialic acid lipid derivative which can be used for modifying a particle preparation and a preparation method and application thereof. The structural general formula of the sialic acid lipid derivative is as shown in the specification, wherein R1 is an H atom or C1-C6 alkyl; R2 is H, (CH2) m or C2-C6 alkenyl, and m =1-17; when X is an H atom or an O atom, R3 is (CH2) n or cholesteryl, and n = 1-17; when X is a carbonyl group, R3 is a C12-C24 alkoxy group, a C12-C24 alkyl substituted amino group or cholesteryl; and R4 is -OH, -NHCOCH3 or -NHCOCH2OH. The sialic acid lipid derivative disclosed by the invention can be used for modifying a particle preparation and realizing different treatment or diagnosis purposes according to the properties of the medicine. Especially in the anti-tumor aspect, the sialic acid lipid derivative can endow a particle preparation with excellent tumor targeting ability to improve the tumorinhibition effect.

The invention relates to the field of biological medicines, and in particular relates to an shRNA (short hairpin ribonucleic acid) for inhibiting expression of human oral cancer cell PRPS2 (phosphoribosyl pyrophosphate synthetase subunit II) as well as construction and application of carrier of the shRNA. The shRNA is shown in SEQ ID NO.1, a target sequence of the shRNA is as whon in SEQ ID NO:2, and is transcribed and generated through a DNA (deoxyribonucleic acid) template sequence shown in SEQ ID NO.3; the template sequence and a linear carrier are recombined, and are recombined with an hTERT (human telomerase reverse transcriptase) promoter sequence to obtain an shRNA eukaryotic expression plasmid for inhibiting expression of human oral cancer cell PRPS2. Verification indicates that the eukaryotic expression plasmid carrier can be used for stably and constantly reducing the expression level of mRNA (messenger ribonucleic acid) and protein of the PRPS2, and causing occurrence of cell prolifation inhibition, cell cycle repression and apoptosis, so that the defects of short acting duration, high toxicity and the like of in vitro chemically synthesized siRNA (small interfering ribonucleic acid) can be overcome.

The invention relates to a pH-sensitive tumor targeted recombinant high-density lipoprotein, which is prepared from the following ingredients in parts by weight: 1 to 5 parts of antitumor medicine, 15to 35 parts of phospholipid, 15 to 60 parts of albumin, 1 to 10 parts of cholesterol derivatives and 2 to 6 parts of linoleic acid. The pH-sensitive cholesterol derivatives in the ingredients effectively ensure the structure stability of rHDL in the blood circulation conveying process; the targeted conveying efficiency of the antitumor medicine to the tumor tissues is improved; after the rHDL istaken by tumor cells; acetal bonds in the pH-sensitive cholesterol derivatives are hydrolyzed into the original cholesterol; the catalysis condition of intracellular ACAT enzyme is met; the fast release of the antitumor medicine in the tumor cells is realized through the lipoprotein structure change; the tumor cells are effectively killed. The lipoprotein belongs to a tumor targeted carrier with huge development potential; the problems of low bioavailability and low tumor killing selectivity of the antitumor medicine in the prior art are solved.

The invention discloses an attenuated salmonella typhimurium mutant strain with STM3120 genes knocked out and application thereof. The attenuated salmonella typhimurium mutant strain is a polynucleotide fragment with attenuated salmonella typhimurium VNP20009 knocked out, the sequence of the polynucleotide fragment is SEQ ID NO:2, and the polynucleotide fragment is replaced with a polynucleotide fragment with the sequence of SEQ ID NO:3. Application of the attenuated salmonella typhimurium mutant strain with the STM3120 genes knocked out in targeted mouse melanoma is disclosed. The mouse melanoma targeted attenuated salmonella typhimurium mutant strain which is high in targeting performance, brand-new, safe, low in price and convenient to use and application thereof are provided.

The invention belongs to the technical field of biological medicine, and particularly relates to a tissue-specific expression circular RNA molecule, a cyclized precursor RNA molecule, a recombinant nucleic acid molecule, a recombinant expression vector, a recombinant host cell, a composition, a pharmaceutical preparation and application of the tissue-specific expression circular RNA molecule, the cyclized precursor RNA molecule, the recombinant nucleic acid molecule, the recombinant expression vector, the recombinant host cell, the composition and the pharmaceutical preparation in preparation of drugs for preventing or treating diseases. And a method of preventing or treating a disease. According to the circular RNA molecule provided by the invention, the coding region is operably connected with the expression regulation element, so that specific high expression of a target polypeptide in a target cell or a target tissue and low expression of the target polypeptide in a non-target cell or a non-target tissue are realized, and the circular RNA molecule has high tissue expression specificity; a safe and effective treatment strategy is provided for clinical targeted treatment of diseases such as tumors.

The invention discloses a novel lipid material for realizing the delivery of a breast cancer targeted drug. The novel lipid material takes lysine as a connecting group and is connected with a cholesteric part, a biotin part and a glucose part. The affinity between biotin and glucose in the novel lipid material and biotin transporter (SMVT) and glucose transporter (GLUT1) can be utilized to realizethe double targeting function to breast cancer and play a stronger breast cancer targeting therapeutic role, wherein the biotin transporter (SMVT) and the glucose transporter (GLUT1) are highly expressed on the surface of breast cancer cells. The novel lipid material can be used in different dosage forms comprising liposomes, nanoparticles, micelles and the like, and the prepared paclitaxel-loaded liposome has obvious breast cancer targeting property and a wide application prospect.

The invention provides an albumin-combined taxol long-circulation nano-particle freeze-dried preparation. Compared with a conventional taxol injecting solution and conventional albumin-combined taxol long-circulation nano-particles, the albumin-combined taxol long-circulation nano-particle freeze-dried preparation can improve a targeting performance of taxol on tumor, is enhanced in effects and is reduced in toxic and side effects. The invention also provides a preparation method of the albumin-combined taxol long-circulation nano-particle freeze-dried preparation.

The invention discloses a porphyrin dimer salt complex loaded with targeting polypeptide-modified ferritin nanoparticles and a use and a preparation method thereof; the complex has the structure of R-Fn-porphyrin dimer salt, wherein Fn is ferritin, and R is a targeting polypeptide; the ferritin is chemically modified by the targeting polypeptide, and the porphyrin dimer salt is wrapped by the targeting polypeptide-modified ferritin. The preparation method comprises the steps: adjusting the pH value of a PBS solution of R-Fn to 2-3 with HCl, then adding the porphyrin dimer salt, mixing and carrying out a reaction for 20-40 min, then adjusting the pH value of the mixed liquid to 7-8, continuing to stir for 1-3 h, filtering with a filter, and thus obtaining the R-Fn-porphyrin dimer salt complex. The invention provides the novel diagnosis and treatment integrated complex having good biological compatibility, having high targeting property on tumor and having combined treatment of PDT and PTT.