35results about How to "Achieve active targeting" patented technology

The invention relates to modification of a cell penetrating peptide for realizing a low-toxicity administration system with a positive targeting selecting function. A shielding peptide, an enzymolysis substrate peptide and a cell-penetrating peptide are connected in sequence, so that an activatable cell penetrating peptide is formed; and a medicament and / or a tracer and / or a medicament carrier is connected or embedded or adsorbed to the cell penetrating peptide, so that an administration system is constructed. According to a shielding peptide sequence, positive charges carried on the surface of the administration system can be reduced or completely neutralized, the cell penetrating capability of the cell penetrating peptide is shielded, and the toxicity of the administration system on normal cells of an organism is lowered; and an enzymolysis substrate peptide sequence can be identified by enzyme systems secreted specifically by different pathological change tissue cells and fractured by enzyme hydrolysis, so that a cell penetrating peptide is released and is used for carrying a medicament and / or a medicament carrier through a cell membrane, and the medicament enters cells and is brought into play. The invention aims to actively convey an antitumor medicament to tumor tissues in a targeted way and make the antitumor medicament enter tumor cells to a larger extent by using the administration system which can be used for activating a cell penetrating function, so that the toxicity at a non-tumor position is lowered while the antitumor effect of the medicament is enhanced.

The present invention relates to a quercetin long-acting liposome powder injection and its preparation method. Said powder injection is formed from quercetin, polyethylene glycol-ethanolamine phosphoglycerides, lecithin, cholesterol and excipient. Said invention also provides the concrete steps of its preparation method.

The invention relates to the field of pharmacy and provides a preparation method of targeting and photo-thermal integrated erythrocyte bionic nanoparticles. The method comprises the following steps: firstly, extracting erythrocyte membranes, then loading indocyanine green to a polylactic acid-hydroxyl acetic acid solution, burying adriamycin amycin to the system, and preparing an indocyanine greenpolylactic acid-hydroxyl acetic acid solution buried with adriamycin amycin through a secondary emulsification-solvent evaporation method; then carrying out a reaction on folic chitosan oligosaccharide and the indocyanine green polylactic acid-hydroxyl acetic acid solution to obtain an adriamycin amycin-folic chitosan oligosaccharide-indocyanine green-polylactic acid-hydroxyl acetic acid solution; and finally, extruding the adriamycin amycin-folic chitosan oligosaccharide-indocyanine green-polylactic acid-hydroxyl acetic acid solution into the erythrocyte membranes to obtain the erythrocyte bionic nanoparticles.

The invention provides a target hydrophilic polymer-triptolide conjugate (I), wherein P represents a water-soluble polymer; D represents triptolide; T represents a target molecule; and L and Z represent linking groups. The conjugate improves water solubility of triptolide, reduces toxicity of triptolide and prolongs circulating half-life period of triptolide in a living body.

The invention belongs to the technical field of nano materials, and in particular relates to carboxymethyl chitosan nanoparticles modified with glycyrrhizic acid, as well as a preparation method and application thereof. The nanoparticles disclosed by the invention are in a core-shell type; a hydrophobic polymer serves as a kernel packaged medicament; and carboxymethyl chitosan serves as a hydrophilic shell and is covalently linked with hepatic targeting ligand glycyrrhizic acid. The preparation method comprises the following steps of: firstly grating and copolymerizing carboxymethyl chitosan and hydrophobic monomers and self-assembling to form nanoparticles in the action of an initiator; secondly, oxidizing glycyrrhizic acid to obtain a glycyrrhizic acid aldehyde solution, mixing the glycyrrhizic acid aldehyde solution with the nanoparticles at a certain proportion and introducing targeting groups, and carrying out ultrasonic loading on the medicament. Compared with the prior art, the preparation method is simple and easy to control and has good repeatability and better stability and safety; and the targeting property and the tumor-inhabiting effect of the anti-tumor medicament can be strengthened remarkably. The nanoparticles serve as a targeting delivery vector for hydrophobic medicaments or molecular probes and can be used for treatment and diagnosis of liver diseases.

The invention discloses a polylysine oligomer modified recombined apoferritin nanometer cage and a preparation thereof. The nanometer cage is a recombined apoferritin cage with the surface modified by polylysine oligomer that is acquired in the manner of self-assembling protein subunits into hollow spherical protein and utilizing a genetic recombination expression technique to modify different amount of lysine at the N terminal of the protein subunits. The protein nanometer cage can realize the depolymerization and recombination of the protein subunits by changing the solution pH so as to realize the drug loading; the biocompatibility and the in vivo stability are high; the nanometer cage can specifically recognize the high-expression transferrin receptor on the tumor cell surface, so as to realize the active targeting; after the recombined apoferritin nanometer cage is introduced into the cells under the endocytosis effect, the lysosome escape is realized through the proton sponge effect under the lysosome acid environment under the effect of polylysine residue, so that the drug in the protein cage can be protected from being degraded in the lysosome; the recombined apoferritin nanometer cage is expected to have an excellent application prospect at the aspects of gene drug delivery, drug organelle targeting delivery, and the like.

The invention relates to a drug carrier with an end group modified by a hydrogen sulfide fluorescent probe as well as preparation and an application thereof and belongs to the field of preparation of drug carriers. The drug carrier provided by the invention and an antitumor drug are self-assembled into a nano-drug co-transporter. The hydrogen sulfide fluorescent probe containing an azide group is on the surface of the nano-drug co-transporter, so that the surface of the nano-drug co-transporter is negatively charged. After the nano-drug co-transporter reaches a tumor part, the azide group in the fluorescent probe is reduced by hydrogen sulfide generated by tumor cells into an amino group, and the change of fluorescence color can be observed under ultraviolet light, so that the selective rapid detection of the hydrogen sulfide is realized; meanwhile, the amino group enables charges on the surface of the nano-drug co-transporter to overturn, a large amount of positive charges generates a positive charge attraction effect with negative charges on the surfaces of the tumor cells, and by means of an active targeting effect of the positive charges, the antitumor drug on the nano-drug co-transporter is quickly transported into the tumor cells; therefore, the targeted drug delivery is realized.

The present invention relates to a magnetic nanoparticle of a fat-soluble photosensitizer and a preparation method thereof; the present invention is the composite nanoparticle with the size of 5nm to 300nm which consists of 30 percent to 70 percent polysaccharide polymer, 5 percent to 40 percent fat-soluble photosensitizer and 10 percent to 50 percent iron-containing magnetic particles which have the magnetic response under the function of external magnetic field. The preparation method thereof is that the polysaccharide polymer is dissolved in alkaline solution, the emulsifier is added, the organic solvents which dissolves the fat-soluble photosensitizer are dropped during the agitating, so as to form the emulsion; the hydrate of ferrous salts and ferric salts is dropped into the emulsion during the agitating, so as to generate the black precipitate, then the magnetic nanoparticle of the fat-soluble photosensitizer can be obtained through the heating, pH valve regulation, getting the solid phase, washing, freezing and drying sequentially. The present invention has the advantages of safety, no toxicity, strong magnetic response and good biological acceptability, can entirely achieve the intravenous administration and significantly improve the targeting of the tumor under the magnetic guide function, so as to improve the photosensitive activity of the photosensitizer and achieve the purposes of reducing the dosage and lowering the toxic and side effects.

The invention relates to preparation and application of a cotransport system of a Mn<2+> donor and chloroquine drugs. According to the preparation and the application, the problems of low pesticide effect, large required dosage, poor targeting ability and serious toxic and side effects of tumor treating drugs can be effectively solved. According to the technical scheme, double-layer hollow mesoporous manganese sesquioxide nanoparticles are synthesized by virtue of a hydrothermal method, hyaluronic acid and the double-layer hollow mesoporous manganese sesquioxide nanoparticles are linked through chemical bonds so as to spontaneously form a nano-layer in a water medium, and then a chloroquine anti-tumor drug enters mesoporous structures of the double-layer hollow mesoporous manganese sesquioxide nanoparticles through a physical effect. According to the drug-cooperated cotransport system, the dosage and toxic and side effects of the drug can be effectively reduced, the treating efficiency of the drug can be improved, the solubility problem of the drug can be effectively solved, and the effective loading of the drug and the controlled release of the drug at target sites of tumors can be realized; the dispersity and biocompatibility of magnetic carriers are improved, the long circle, the active targeting and the fixed-point gate-controlled release of the drug are realized; and furthermore, the preparation process is simple, energy saving, environmentally friendly and low in cost, the industrial production can be realized, and the preparation process is the innovation of the tumor treating drugs.

The invention relates to reducing response magnetic drug-loaded nanoparticles with synergetic anti-cancer interaction and a preparation method of the reducing response magnetic drug-loaded nanoparticles. The drug-loaded nanoparticles are prepared from a polymer prodrug and inorganic nanoparticles, which are connected through a disulfide bond; and the inorganic nanoparticles include surface-aminated superparamagnetism ferroferric oxide nanoparticles (SPION-NH2) and aminated selenium nanoparticles (NH2-R-SeNPs) employing an amino-containing high polymer as a template. The preparation method specifically comprises the following steps: (1) mixing an SPION-NH2 solution with an NH2-R-SeNPs dispersing liquid and adjusting the pH value to be 4.5-5.5; (2) dissolving the polymer prodrug connected through the disulfide bond by using ultrapure water and adjusting the pH value to be 5; and (3) dropwise adding the solution obtained in step (1) to the solution obtained in step (2), adjusting the pH value of a system to be 7.4, stirring the solution at room temperature for 10-14h to obtain the reducing response magnetic drug-loaded nanoparticles with synergetic anti-cancer interaction. The drug-loaded nanoparticles have the advantages of specific responsiveness in a targeted area, synergetic interaction and a low toxic or side effect.

The invention provides a preparation method and application of a metal organic framework drug-loaded nano system based on a small molecule drug, MIT and HYD are jointly loaded in pores of a metal organic framework ZIF-8 through a simple and rapid method to prepare nano particles, and active targeting HA modification of tumor cells is realized. The problems of poor stability of MIT and HYD and co-delivery of MIT and HYD are solved, and the immune efficacy of chemotherapeutic drugs is enhanced. The (M+H) (at) ZIF / HA intravenous injection preparation is low in toxicity, good in safety, high in tumor cell toxicity and obvious in solid tumor inhibition effect.

The invention relates to a self-assembled material capable of forming a nano defense network in situ on a tumor as well as a preparation method and an application of the self-assembled material, the self-assembled material is composed of a targeting peptide, a self-assembled polypeptide and a dipyrene fluorescence signal molecule, and the chemical structure of the self-assembled material is shownas a formula (I); R1 is from a self-assembled polypeptide with multiple hydrogen bonds in a molecule; and R2 is from a tumor targeting peptide. The preparation method comprises the step of synthesizing the self-assembled material by taking amino acid with protected terminal amino and side chain amino and a dipyrene fluorescence signal molecule as raw materials through a solid-phase synthesis method. The tumor site can be actively targeted; a tumor part can be induced to deform; according to the preparation method, a nanofiber network structure is formed through self-assembly, namely a nano defense network can be formed in situ in a tumor, so that tumor cells are released to induce capture of vascular endothelial growth factors generated by new blood vessels, generation of new blood vesselsis prevented, nutrient supply of the tumor is cut off, and meanwhile, a metastasis path of the tumor is also blocked.

The invention relates to a gadolinium-containing macromolecular contrast agent HA-DTPA-Gd for specific imaging of a lymphatic system and a preparation method thereof. The molecular structure of the contrast agent is shown in the specifications. A macromolecular magnetic resonance imaging (MRI) contrast agent prepared by the method has a high molecular weight and is mainly absorbed by capillary lymph ducts but cannot enter blood capillaries after interstitial administration; and simultaneously, hyaluronic acid molecules are taken as the main chain of the contrast agent so that the contrast agent is easily absorbed by a lymphatic endothelial hyaluronic acid receptor LYVE-1 in the capillary lymph ducts to enter the lymphatic system. Therefore, the contrast agent has the advantages of realizing active targeting of lymph, avoiding the disturbance of the capillary lymph ducts in the MRI of the lymphatic system and improving the sensitivity and specificity of lymph qualitative diagnosis.

The invention relates to a self-assembly material for in-situ construction of an artificial extracellular matrix, and a preparation method and application thereof. The self-assembly material is composed of a targeting peptide, a self-assembly polypeptide and a dipyrene fluorescence signal molecule, and the chemical structure of the self-assembly material is shown as a formula (I); wherein R1 is from a self-assembled polypeptide with multiple hydrogen bonds in a molecule; r2 and R3 are both from a tumor targeting peptide. The preparation method comprises the step of synthesizing the self-assembled material by taking amino acid and dipyrene fluorescence signal molecules as raw materials through a solid-phase synthesis method. The self-assembly material can actively target a tumor site; meanwhile, the tumor part can be induced to deform; the artificial extracellular matrix is connected with a natural extracellular matrix to jointly form a long-term barrier to inhibit tumor metastasis andinvasion, and the artificial extracellular matrix and the natural extracellular matrix can compete for binding sites of integrin, reduce expression of metal matrix protease and better inhibit tumor metastasis.

The invention provides a mixed medicament carrying micelle based on polyphosphoester, a preparation method thereof and a mixed medicament carrying micelle modified by a positive targeted group. A compound micelle consists of polyphosphoester-polylactic acid two segmented copolymers and polyethylene glycol-polylactic acid two segmented copolymers; the compound micelle with the same polylactic acid hydrophobic kernel and different hydrophilic shells is formed under the hydrophobic interaction of polylactic acid segments. The mixed medicament carrying micelle provided by the invention has the advantages of high hydrophilicity and high stability, is easy to perform targeted modification, has an in vivo long circulation effect, effects of facilitating of targeted cell endocytosis and in-cell medicament release, targeted modified mixed medicament carrying micelle can achieve a passive targeting effect and a positive targeting effect, so that the tumor treatment effect is further improved.

The invention discloses a construction method of a magnetic resonance molecular probe for targeted-marking MMP-2, wherein the novel molecular probe for MRI diagnosis of glioma is prepared from superparamagnetic iron oxide nanoparticles (USPIO) and matrix metalloproteinase-2 antibody (MMP2Ab) by using a diimide method. Compared with the prior art, the method has the advantages that the USPIO-PEG-MMP2Ab not only has higher magnetic saturation intensity and relaxation rate, but also has good biocompatibility; after intravenous administration, the USPIO-PEG-MMP2Ab can actively target glioma cellsto generate obvious negative contrast effect on magnetic resonance T2WI; and qualitative and hierarchical diagnosis of brain glioma is finished through magnetic resonance molecular imaging.

The invention relates to the field of medical materials, and discloses a preparation method of doxorubicin nanoparticles with folate-modified chitosan as a carrier. The preparation method includes thesteps that firstly, folate active ester is prepared, and the folate-modified chitosan is obtained by an amide reaction; a prepared doxorubicin solution and a polydopamine solution are added to a folate-modified chitosan solution, and doxorubicin-folate-chitosan is obtained; and finally, a nucleic acid aptamer AS1411 is mixed with the doxorubicin-folate-chitosan, centrifuged, frozen and dried to obtain the doxorubicin nanoparticles with the folate-modified chitosan as the carrier. According to the preparation method, through preparation of polymer nanoparticles embedded with anticancer drugs,an efficient therapeutic method integrated with tumor thermotherapy and targeting can be realized, the stability of the drugs is improved, active targeting is achieved, the ability to bind to a receptor is improved, and thus the therapeutic effect on cancer cells is greatly improved.

The invention relates to the technical field of medicine. At present, a USPIO (Ultra-small Super Paramagnetic Iron Oxide) preparation which has high in-vivo target tissue selectivity, high target tissue distribution concentration and high MR (Magnetic Resonance) imaging sensitivity is not reported. A stable and effective invisible nano-liposome preparation is prepared by taking an invisible nano-liposome as a vector, combining MR diagnosis with treatment and carrying USPIO and an anti-tumor medicament simultaneously. Due to the adoption of the invisible nano-liposome injection preparation serving as an MR contrast agent, the in-vivo tissue selectivity of the USPIO can be increased, the sensitivity is increased, and early diagnosis of diseases is facilitated; meanwhile, the invisible nano-liposome injection preparation is taken as a means for evaluating the curative effect of tumor therapy, so that the curative effect of tumor chemotherapy is monitored in real time, overtreatment of a patient is reduced, toxic and side effects are reduced, and the curative effect of tumor chemotherapy is improved.

The invention discloses a folic acid receptor-mediated in-tumor environment-sensitive doxorubicin albumin nanoparticle and a preparation method. An amino group and a carboxyl group are condensed and subjected to acylation reaction, and folic acid is linked to albumin; after a one-pot amide reaction, histamine is mixed with a folic acid-albumin solution to obtain a folic acid-targeted and pH-sensitive folic acid-albumin-histamine modifier; glutathione is used for opening a disulfide bond in the folic acid-albumin-histamine, and mixed with doxorubicin at alkaline pH to achieve spontaneous cross-linking of the intermolecular disulfide bond and to obtain the folic acid receptor-mediated pH-and-glutathione-sensitive albumin doxorubicin nanoparticle. The nanoparticle provided by the invention has an approximate spherical shape and strong uniformity, the particle size of about 70 nm, a small dispersion coefficient, good stability, and high drug loading and embedding rate of doxorubicin; underthe double stimulation of pH and glutathione, a drug can be quickly released, and the important application value is achieved in targeted drug delivery to tumors.

The invention relates to a composite nano-microsphere with a rapid mucus permeation effect as well as a preparation method and an application of the composite nano-microsphere. The composite nano-microsphere comprises a metal organic framework ZIF-8 and a hydrophilic high-molecular polymer modified on the surface of the metal organic framework ZIF-8, the metal organic framework ZIF-8 is loaded with black phosphorus quantum dots and active ingredients, and the hydrophilic high-molecular polymer is selected from polyethylene glycol. According to the invention, ZIF-8 is modified by hydrophilic PEG for the first time and is used for increasing the mucus penetration capability of ZIF-8, so that the mucus penetration capability of the composite nanoparticles is improved, and the targeting capability and the capability of penetrating through human physiological barrier obstruction are improved.

The invention belongs to the technical field of medicines and particularly relates to a preparation method for a pH-sensitive carbon nano tube-targeted drug delivery system. The preparation method comprises the following steps: adopting a carbon nano tube which is oxidized by adopting mixed acid as a carrier, loading an anti-tumor drug on the surface of the carbon nano tube by virtue of Pi-Pi effect; and then, adopting chitosan coupled by RGD (arginine-glycine-aspartic acid) to further modify the surface of the carbon nano tube to obtain a pH-sensitive carbon nano tube-targeted drug delivery carrier. The carbon nano tube carrier is high in drug loading capacity, the drug is delivered to tumor cells by virtue of dual effects of chitosan modification and RGD-targeted guiding, so that the drug is promoted to release in a low-pH tumor cell environment, and thus, the drug concentration in tumor tissue is increased, the tumor cells are killed, the anti-tumor effects are increased, and the toxic and side effect is lowered. The preparation method disclosed by the invention is simple in operation, gentle in preparation condition, easily available and reliable to obtain products, simple in posttreatment, and suitable for industrial production.

The invention relates to a metal nano-cluster containing radioactive metal nuclide, a nano-material, a preparation method of the nano-cluster and the nano-material and application of the nano-cluster and the nano-material in preparation of and the metal nano-cluster containing the radioactive metal nuclide is characterized in that the metal nano-cluster containing the radioactive metal nuclide comprises the radioactive metal nuclide and a metal nano-cluster; and the radioactive metal nuclide is doped in the metal nano-cluster. According to the metal nano-cluster containing the radioactive metal nuclide, the nano-material containing the radioactive metal nuclide, the preparation methods of the nano-cluster and the nano-material and the application of the nano-cluster and the nano-material in preparation of targeted drugs, nuclide labeling based on the metal nano-cluster and without chelating agent ligands is achieved, the influence of the chelating agent ligands on in-vivo behaviors of the nano-drugs is avoided, and the stability of nuclide labeling is enhanced. According to the invention, various radioactive metal nuclides are individually or simultaneously labeled, and the application of the radioactive metal nuclides in radioactive nano-drugs is broadened. According to the method, nuclides can still be efficiently labeled under the large-system condition, and large-batch synthesis of radioactive nano-drugs is promoted.

The invention relates to the technical field of medicine. At present, a USPIO (Ultra-small Super Paramagnetic Iron Oxide) preparation which has high in-vivo target tissue selectivity, high target tissue distribution concentration and high MR (Magnetic Resonance) imaging sensitivity is not reported. A stable and effective invisible nano-liposome preparation is prepared by taking an invisible nano-liposome as a vector, combining MR diagnosis with treatment and carrying USPIO and an anti-tumor medicament simultaneously. Due to the adoption of the invisible nano-liposome injection preparation serving as an MR contrast agent, the in-vivo tissue selectivity of the USPIO can be increased, the sensitivity is increased, and early diagnosis of diseases is facilitated; meanwhile, the invisible nano-liposome injection preparation is taken as a means for evaluating the curative effect of tumor therapy, so that the curative effect of tumor chemotherapy is monitored in real time, overtreatment of a patient is reduced, toxic and side effects are reduced, and the curative effect of tumor chemotherapy is improved.

The present invention relates to a magnetic nanoparticle of a fat-soluble photosensitizer and a preparation method thereof; the present invention is the composite nanoparticle with the size of 5nm to 300nm which consists of 30 percent to 70 percent polysaccharide polymer, 5 percent to 40 percent fat-soluble photosensitizer and 10 percent to 50 percent iron-containing magnetic particles which havethe magnetic response under the function of external magnetic field. The preparation method thereof is that the polysaccharide polymer is dissolved in alkaline solution, the emulsifier is added, the organic solvents which dissolves the fat-soluble photosensitizer are dropped during the agitating, so as to form the emulsion; the hydrate of ferrous salts and ferric salts is dropped into the emulsion during the agitating, so as to generate the black precipitate, then the magnetic nanoparticle of the fat-soluble photosensitizer can be obtained through the heating, pH valve regulation, getting thesolid phase, washing, freezing and drying sequentially. The present invention has the advantages of safety, no toxicity, strong magnetic response and good biological acceptability, can entirely achieve the intravenous administration and significantly improve the targeting of the tumor under the magnetic guide function, so as to improve the photosensitive activity of the photosensitizer and achieve the purposes of reducing the dosage and lowering the toxic and side effects.

The invention discloses a folic acid receptor-mediated tumor internal environment sensitive doxorubicin albumin nanoparticle and a preparation method. Condensation and acylation of amino and carboxyl groups to link folic acid to albumin; followed by a one-pot amide reaction to mix histamine with folic acid-albumin solution to obtain folic acid-albumin-histamine with folic acid targeting and pH sensitivity Modifier; use glutathione to open the disulfide bond inside folic acid-albumin-histamine, mix it with doxorubicin at alkaline pH, realize the spontaneous cross-linking of intermolecular disulfide bond, and obtain the folic acid receptor-mediated Guided pH- and glutathione-sensitive albumin doxorubicin nanoparticles. The nanoparticle provided by the present invention has a nearly spherical appearance and strong uniformity, a particle diameter of about 70nm, a small dispersion coefficient, good stability, and high drug loading and embedding efficiency of doxorubicin; The rapid release of drugs can be achieved under the dual stimulation of glutathione, which has important application value in the targeted delivery of drugs to tumors.

The invention relates to a composite nano-microsphere with rapid mucus penetration and its preparation method and application, and specifically discloses a composite nano-microsphere, which includes a metal-organic framework ZIF-8, and a surface modification of the metal-organic framework ZIF-8 The hydrophilic high molecular polymer, the metal organic framework ZIF‑8 is loaded with black phosphorus quantum dots and active ingredients, and the hydrophilic high molecular polymer is selected from polyethylene glycol. In the present invention, for the first time, ZIF-8 is modified with hydrophilic PEG and used to increase its mucus penetration ability, so that the mucus penetration ability of composite nanoparticles is improved, and the targeting ability and ability to penetrate human physiological barrier barriers are improved.