78results about How to "Promote endocytosis" patented technology

A composition for delivering an agent to a cell, comprising a bispecific affinity reagent and a pH-responsive, membrane destabilizing polymer. The bispecific affinity reagent may include a first affinity reagent covalently linked to a second affinity reagent, wherein the first affinity reagent binds to a molecule on the surface of a cell, and the second affinity reagent binds to an intracellular target.

The invention relates to a gold-gadolinium composite nano material as well as a preparation method and application of the gold-gadolinium composite nano material. The gold-gadolinium composite nano material provided by the invention comprises an inner core of a gold nano rod modified by silicon dioxide, and a gadolinium-containing silicon dioxide layer covering the outer side of the inner core. The gold-gadolinium composite nano material is high in gadolinium contain and each nano particle contains 1.5*10<6> Gd ions; the gold-gadolinium composite nano material is good in imaging effect and small in toxic side effect and can be used for loading a plurality of types of drugs and probe molecules, and target molecules can be adsorbed on the surface of the gold-gadolinium composite nano material, so that the drugs and the molecules can be efficiently transported to focus parts and multifunctional diagnosis and treatment can be realized. After the gold-gadolinium composite nano material is used as a carrier for loading the drugs, the gold-gadolinium composite nano material has the synergistic effect of thermal therapy and chemical therapy under laser irradiation in a treatment process of tumor-bearing mice, so that the growth of tumors is effectively inhibited; the gold-gadolinium composite nano material has multiple imaging functions including CT (Computed Tomography), MRI (Magnetic Resonance Imaging), photo-acoustic imaging and the like, and is suitable for being applied to complicated need tumor diagnosis and treatment.

The invention discloses a nano hydroxyapatite-gene-medicament complex as well as a preparation method and application thereof, belonging to the field of biomedicine. The complex disclosed by the invention comprises nano hydroxyapatite, anti-tumor genes and an anti-tumor medicament, wherein the size of nano hydroxyapatite is 20-300nm, the genes are anti-tumor genes and the medicament is an anti-tumor medicament. The preparation method comprises the following steps: mixing a calcium salt with a phosphate solution to prepare nano hydroxyapatite, adsorbing the anti-tumor genes to form a nano hydroxyapatite-gene precursor complex and further adsorbing the anti-tumor medicament by the precursor complex to form the complex, wherein the complex can efficiently pass through cancer cell membranes and promote the apoptosis of cancer cells. Hydroxyapatite with good biocompatibility is used as a co-transfer carrier, thereby having high safety, high loading rate of the genes and the medicament, high transfection efficiency and great effect of killing the cancer cells. Taking nano-hydroxyapatite as the co-transfer carrier of the genes and the medicament has great application prospects in the field of treatment of cancers.

The invention provides a salidroside segmented copolymer lipid nanoparticle preparation for intravenous injection and a preparation method of the nanoparticle preparation, as well as application of the preparation in preparing anti-cancer medicaments. The preparation comprises salidroside, segmented copolymer, lipid and surfactant.

The invention relates to an oridonin cubic liquid crystal nanoparticle and a preparation method thereof. The oridonin cubic liquid crystal nanoparticle is prepared from the following raw materials in percentage by weight: 0.1 to 0.5 percent of oridonin, 7 to 64 percent of amphiphilic lipid material, 6 to 29 percent of solvent, 1 to 8 percent of stabilizer, and 25 to 65 percent of water, wherein the amphiphilic lipid material is glycerol mono-oleate or phytould likeriol; the mass ratio of a liquid crystal material to the stabilizer is 1 to (0.01 to 0.30). The oridonin cubic liquid crystal nanoparticle provided by the invention is smaller in particle size, good in uniformity, and beneficial to endocytosis and transfer of enterocyte; by utilizing a unique structure of cubic liquid crystal, a dissolution barrier and a permeation barrier of the oridonin during an oral absorption process are effectively overcome, the oral relative bioavailability of the oridonin is remarkably improved, and meanwhile, the oridonin can be slowly released.

The invention discloses a quaternary ammonium type cationic starch gene controlled release vector material, and a preparation method and an application thereof; the preparation method particularly comprises the following steps: allowing starch which has a water content of 4.7-13.5% and a weight-average molecular weight of 13000-64000 Da to mix and react with a mixed system of solid caustic soda, water, and a quaternary ammonium type cationic etherifying agent which are stirred and well mixed through an ice water bath in a kneader by a dry method under a condition with a temperature of 25-30 DEG C and a rotating speed of 40-100 r/min for 12-48 hours; after the reaction is completed, washing, drying, and crushing to obtain the quaternary ammonium type cationic starch gene controlled releasevector material. An application of the vector material prepared by the invention as a non-viral vector material in gene therapy realizes the controlled release of gene drugs, improves the drug bioavailability, reduces the toxic and side effect of the drugs and the vector.

The invention relates to the technical field of medicines, and discloses a temperature targeting-based nanogel plasmid compound used for delivering expression gene medicines, and a preparation method thereof. A temperature-sensitive core-shell structured nanogel is synthesized through a free radical coprecipitation technology, and the above carrier adopts temperature-sensitive polyisopropyl acrylamide (PNIPAM) as a core and positively charged polyethyleneimine (PEI) as a shell; and a targeting intelligent nanogel carrier material with high clinic application prospect is prepared through electrostatic adsorption and gene compounding by using high-temperature passive targeting in tumor microenvironment to realize good treatment of tumors by gene medicines. The compound makes a gene carrying administration system be well enriched in a tumor position to improve the gene transfection efficiency, and provides a new treatment mode for gene treatment of tumors.

The invention relates to a HA-targeted layered doubled hydroxide-ultrafine iron nano material and preparation and applications thereof. The preparation is as follows: synthesizing an LDH-Fe3O4 nano composite material by a coprecipitation method; covalently bonding activated hyaluronic acid on the surface of an LDH laminate through a silane coupling agent; and finally, carrying out surface loadingof an anticancer drug. The nano-material particles are uniformly distributed, and can enhance the MR imaging effect of the tumor part in an animal body. The LDH-Fe3O4-HA NPs is used as a carrier of ananticancer drug doxorubicin DOX, not only has sensitive pH response and release characteristics, but also can carry out specific recognition on tumor cells expressed by CD44 receptors so as to achieve the idealization effect of efficiently inhibiting tumors.

The invention relates to antitumor application of chlorambucil-polydopamine prodrug nanoparticles, and concretely relates to a mild photothermal therapy-chemotherapy combined tumor alete treatment technology based on the chlorambucil-polydopamine prodrug nanoparticles. The nanoparticles can realize spatiotemporal manipulation in an antitumor effect in order to achieve accurately-positioned tumor ablation, and passive targeting action of the prodrug nanoparticles on tumor parts can be achieved by the enhanced permeation and retention(EPR) effect; the mild photothermal effect can enhance the expansion of tumor blood vessels and the permeability of cell membrane effectively promote the accumulation and penetration of the nanoparticles in tumors and the endocytosis of tumor cells; and photothermal therapy can induce the antitumor immunity in order to improve the effect of chemotherapy, so synergistic antitumor effects are generated in the photothermotherapy-chemotherapy combined therapy. The application provides a new way for precise cancer treatment, and has a potential clinical application prospect.

The invention discloses a conjugated backbone doped zwitterionic polyfluorene vinylene and preparation and application. The preparation comprises the following steps of: taking dibromofluorene derivative (A monomer), dienyl benzene derivative (B monomer) and dibromoaromatic heterocyclic structure (C monomer) doped with a small amount of narrow band gap, adopting a three-component polymerization method of A+B+C to carry out the Heck reaction of the organic metal catalysis, obtaining a neutral polymer, and obtaining the conjugated backbone doped zwitterionic water-soluble polyfluorene vinylene subjected to the reaction of quaternary and/or acid ester hydrolysis and the like. The synthesis method is simple, and the ratio type fluorescence emission can be achieved with improved detection sensitivity; and the red/near-infrared emission can be achieved, and the fluorescence biological imaging effect can be improved. The zwitterionic structure is beneficial to the endocytosis of the cells, which can effectively improve the adsorption of the material by the cell membrane, so that the better biological imaging effect can be achieved.

The present invention relates to a cell-nucleus-targeted antitumor nanomedicine carrier and a preparation method and application thereof. The cell-nucleus-targeted antitumor nanomedicine carrier comprises polymer micelle NLS-PEG-PAsp (BzA) and a pH-sensitive negatively-charged polymer constructed on the surface of the polymer micelle by electrostatic interaction, the pH-sensitive negatively-charged polymer can changed into positively-charged from negatively-charged when pH is 6.5 to 6.8, the size of the polymer micelle is 20nm-40nm, and the particle size of the nanomedicine carrier is 100nm-110nm. The cell-nucleus-targeted antitumor nanomedicine carrier can stably circulate in body and is effectively enriched in a tumor site through EPR effect. When a nano medicine reaches tumor microenvironment, under the condition of the pH of 6.5-6.8, a negative polymer protective layer compounded on the surface of the polymer micelle is changed into positively-charged from negatively-charged, and further is removed from the surface of nanoparticles of the polymer micelle, the positively-charged polymer micelle facilitates endocytosis, and finally the positively-charged polymer micelle targets tumor nuclei under the action of nuclear localization signal peptide to release the antitumor medicine in the nucleus.

The invention relates to a folate-receptor-mediated pH-sensitive Decoy-ODN (Decoy-oligodeoxynucleotide) nanoparticle preparation and a preparation method thereof. A nanoparticle suspension is prepared from 5-200 mu g/ml of the Decoy-ODN used as a generic medicament, 0.01-6.0 mg/ml of folate-conjugated trimethyl chitosan used as a medicament carrier and 10-500 mu g/ml of pH-sensitive material by a complex coacervation method, wherein the folate conjugation rate of the folate-conjugated trimethyl chitosan is 5-30%, and the ratio of the total volume of the Decoy-ODN solution and the pH-sensitive material solution to the volume of the folate-conjugated trimethyl chitosan solution is 1:(1-4). The folate-receptor-mediated pH-sensitive Decoy-ODN nanoparticle preparation provided by the invention has the advantages of good shaping property, uniform particle size distribution, high DNA (deoxyribonucleic acid) binding rate, better stability, low cytotoxicity and high in-vitro transfection efficiency.

The invention discloses an anti-human ErbB2 bispecific antibody as well as a preparation method and application thereof. The anti-human ErbB2 bispecific antibody provided by the invention is prepared by linking a single chain antibody of anti-human ErbB2 to the N-terminal of the heavy chain of the Trastuzumab antibody through linker peptides; the heavy chain variable region in the single-chain antibody is a heavy chain variable region of an HuA21 antibody; a light chain variable region in the single chain antibody is a light chain variable region of an HuA21 antibody; the amino acid sequence of the linker peptides is the 275th to 289th sites in the sequence I of the sequence table. The anti-human ErbB2 bispecific antibody provided by the invention has a good antitumor effect and has a more excellent endocytosis effect than the original Trastuzumab antibody and the HuA21 antibody, so that the anti-human ErbB2 bispecific antibody is of great significance as used for preparing antibody targeting drugs as a drug carrying tool.

Provided is a method of preparing a stimuli-responsive multifunctional nanoparticle, including in sequence the steps of: (a) conjugating covalently an active targeting moiety to a hydrophilic polymer to form a targeted polymer, (b) conjugating covalently a redox-responsive moiety to the hydrophilic polymer of the targeted polymer to form a targeted redox-responsive polymer, (c) conjugating covalently a pH-responsive moiety of a drug complex to the redox-responsive moiety of the targeted redox-responsive polymer to form a targeted stimuli-responsive polymer-drug conjugate, wherein the drug complex includes a hydrophobic drug covalently linked to the pH-responsive moiety, and (d) adding the targeted stimuli-responsive polymer-drug conjugate and optionally an imaging agent into an aqueous liquid to allow self-assembly into a stimuli-responsive multifunctional nanoparticle, wherein the hydrophobic drug of the stimuli-responsive multifunctional nanoparticle forms a hydrophobic core, and the imaging agent is incorporated within the hydrophobic core.

The invention provides a lysine grafted polyethyleneimine cationic gene vector. The lysine grafted polyethyleneimine cationic gene vector comprises hyperbranched polyethyleneimine and lysine which is grafted on the hyperbranched polyethyleneimine and is protected by p-toluenesulfonyl. In order to realize high-efficiency delivery of a gene vector to a gene, polyethyleneimine with small molecular weight is modified, and lysine protected by p-toluenesulfonyl is grafted on the polyethyleneimine. According to the invention, three PEI-Lys (Tos) carriers with different grafting ratios (1: 5; 1: 10; 1: 15) are prepared. Through comparison, the grafting ratio (1: 10) with the best transfection performance is screened for other subsequent evaluation characterization. Experimental results show that the PEI-Lys (Tos) cationic carrier prepared through modification design has higher transfection efficiency and lower cytotoxicity, and has a huge application prospect in the fields of gene carrier design and tumor resistance.

The invention relates to an ofloxacin liquid crystal nano-particle eye drop and a preparation method thereof. The ofloxacin liquid crystal nano-particle eye drop is prepared from 0.12-0.2% of ofloxacin, 20-50% of at least one neutral lipid and/or tocopherol, 20-50% of at least one phosphatidylcholine, 0.2-20% of a nonionic surfactant, 0.1-10% of at least one solvent, 0.28-0.35% of at least one thickener, and the balance of injection water. The liquid crystal gel nano-particle has a small and uniform particle size, so the endocytosis and the transport of cells are benefited; and the unique adhesion and the liquid crystal phase structure of the liquid crystal gel are used to prolong the retention time of drug active ingredients in eyes and effectively control the release of an entrapped substance, so the bioavailability is improved. Additionally, the preparation method of the ofloxacin liquid crystal gel nano-particle eye drop has the advantages of simple process steps, easiness in industrial large-scale production, and low production cost.

The invention provides ultrafast charge reversible chitosan-based nanogel as well as a preparation method and application thereof, and belongs to the field of biomedicine. The preparation method comprises the following steps: synthesizing a chitosan-polypyrrole polymer, then cross-linking the chitosan-polypyrrole polymer with glutaraldehyde to prepare chitosan-polypyrrole nanogel, and finally, treating the chitosan-polypyrrole nanogel with a NaOH solution to obtain a series of chitosan-polypyrrole-hydroxyl nanogel. The prepared ultrafast charge reversible chitosan-based nanogel can realize rapid conversion of pH-induced surface charges, has good cell compatibility, good protein resistance, relatively high anti-cancer drug loading efficiency and relatively good anti-tumor ability, and is hopeful to be used as a safe and promising nano-carrier to construct a low-side-effect enhanced anti-tumor treatment platform, and is applied to the field of biomedicine.

The invention discloses the use of a protein in preparation of drugs for prevention and treatment of Alzheimer's disease. The amino acid sequence of the protein is shown as SEQ ID NO:2, the protein contains the extracellular fragment 1-171th amino acids of TREM2 receptor protein, and the nucleotide sequence is shown as SEQ ID NO:1. The protein can increase the density of microglial cells, promotethe endocytosis and degradation of microglial cells to Abeta (Amyloid-beta), reduce the intracerebral Abeta level and the deposition of Abeta amyloid plaques, increase the long-term potentiation of CA3-CA1 in the mouse hippocampus region, and strengthen the learning and memory ability of mice.