89 results about "Folate targeting" patented technology

The invention relates to a preparation method of a CT/MR bimodal imaging nano contrast medium with a folate targeting function. The method comprises the following steps of: (1) preparing FA-PEG-COOH; (2) modifying the dendrimer by use of DOTA-NHS, COOH-PEG-FA and mPEG-COOH to obtain the pegylation dendrimer modified by DOTA and folate; and (3) adding chloroauric acid solution, NaBH4 solution and Gd(NO3)3.6H2O into the dendrimer solution obtained in the step (2), then adding triethylamine and acetic anhydride, and after reaction, performing dialysis and freeze-drying. The preparation method provided by the invention is simple and easy to operate, and has mild reaction conditions and prospects for industrial implementation; and the CT/MR bimodal imaging nano contrast medium has better water solubility and stability, realizes a specific targeting function for the folate receptor high-expression cancer cell, and is expected to be applied to early detection of tumor.

The present invention relates to compounds, compositions, kits, and methods of use in targeting nucleotides, such as siRNA's, to cancer cells or to immune system cells involved in inflammation. More particularly, the invention is directed to receptor binding ligand-nucleotide delivery conjugates for use in specifically targeting the conjugates to cancer cells or to immune system cells, methods of treatment with these conjugates, methods of preparation of these conjugates, and methods of reducing the expression of a gene in vitro or in vivo with the conjugates described herein.

The invention relates to a folic acid coupled targeted ferriferrous oxide/mesoporous silica/copper sulfide nano-composite particle as well as a preparation method and an application thereof. The nano-composite particle consists of Fe3O4@mSiO2 core-shell structural nanoparticles, wherein the core-shell structural nanoparticles take Fe3O4 nanoparticles as cores and mSiO2 as shells, and copper sulfide nanoparticles and folic acid cover the surfaces of the shells; the folic acid is grated on one part of the mesoporous silica (mSiO2) and the copper sulfide particles are loaded on the other part of the mesoporous silica; and polyethylene glycol is grated on the surface of the copper sulfide nanoparticles. Compared with the prior art, the nano-composite particles disclosed by the invention has a broad application prospect in the aspects of nuclear magnetic resonance imaging, drug loading and photothermal therapy; anti-cancer drugs and photothermal reagents can be transmitted to tumor parts in a targeted mode; the nano-composite particle can reduce toxic and side effects on normal tissues and cells, and meanwhile, the nano-composite particle can effectively kill cells, so that a treatment effect is further improved; and moreover, the nano-composite particle is relatively low in preparation condition demand and cost.

The invention discloses a targeting mesoporous polydopamine multi-purpose nanometer diagnosis and treatment preparation as well as a preparation method and applications of the targeting mesoporous polydopamine multi-purpose nanometer diagnosis and treatment preparation. The targeting mesoporous polydopamine multi-purse nanometer diagnosis and treatment preparation is composed of a water-soluble folic-acid-targeting mesoporous polydopamine medicine carrier, hydrophobic regorafenib and manganese sulfate, wherein the mass ratio of regorafenib to the folic-acid-targeting mesoporous polydopamine medicine carrier is (0.5-4): 1, and the mass ratio of manganese sulfate to the folic-acid-targeting mesoporous polydopamine medicine carrier is (1-6):1. The targeting mesoporous polydopamine diagnosis and treatment preparation can recognize positive tumor cells of a folic acid receptor, so that a targeting effect is achieved during treatment. For the diagnosis and treatment preparation, the chemotherapy under the guidance of MRI imaging is realized, the tumor treatment effect is expected to be improved, meanwhile, the biocompatibility is good, and therefore, the targeting mesoporous polydopaminemulti-purpose nanometer diagnosis and treatment preparation has the clinical application potential.

The invention belongs to the technical field of biological medicine, and specifically relates to a glutathione/pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel, a preparation method thereof, and applications of the glutathione/pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel as a drug carrier. According to the preparation method, methacrylic acid, acrylic acid, and acrylamide are taken as monomers; zinc dimethacrylate and calcium dimethacrylate are taken as cross-linking agents; and refluxing precipitation is carried out in acetonitrile solvent so as to prepare a nano-hydrogel with high uniformity and low dispersity; and then a folate-targeted polyethylene glycol-modified nano-hydrogel is obtained via reaction of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride/N-hydroxy succinimide with polyethylene glycol-folic acid molecules which are modified via amination. The glutathione/pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel shapes like balls with regular morphology, is uniform in size, possesses glutathione and pH double stimulus responsiveness; particle size can be adjusted; no obvious deposition is observed after long-term uniform dispersion in water; colloidal stability and dispersibility are excellent; and the glutathione/pH double stimulus responsive ionic-crosslinked polymer nano-hydrogel is an ideal drug carrier.

The invention discloses a folate-targeted hydrophobic medicine-loaded polymeric vesicle and a preparation method and use thereof. The polymeric vesicle is prepared by the following steps of: (1) dissolving amphiphilic triblock copolymer and a hydrophobic medicine in an organic solvent, adding distearamide phosphatidyl ethanolamine-polyethylene glycol (2000) folate, evaporating to remove the organic solvent to prepare a uniform thin film, blowing and drying; and (2) adding double distilled water and products in the step (1) into a container, hydrating, shaking and uniformly mixing to ultrasonically form stable emulsion, performing film filtering, collecting filter liquor and performing freeze drying, The polymeric vesicle has main advantages of liposome, nanoparticles and other particle medicine-loaded systems, stability in vivo and in vitro obviously superior to the liposome, thicker film layer, contribution to encapsulating the hydrophobic medicine, dual-targeting function of EPR passive targeting and folate active targeting, and capacity of making the medicine-loaded vesicle effectively targeted and gathered on a tumor part and fulfilling the aim of targeted therapy.

The invention provides an amphiphilic block copolymer having folate-targeted pH-reduction dual-response and antineoplastic activity and preparation as well as application thereof; through RAFT polymerization, a functionalized disulfide monomer, methoxy polyethylene glycol responding by acid stimulation and functionalized folic acid form a macromolecular block copolymer, i.e. a disulfide monomer-acidity PEG-folic acid copolymer, being good in biocompatibility. The copolymer has pH and reduction dual stimulus-response, and is provided with a folic acid active targeting polymer drug carrying micelle, and can effectively release adriamycin amycin at a target site. The micelle with intelligent responsibility has low cytotoxicity, is biodegradable, has a proper drug carrying level, and can promote a great quantity of drugs to be more quickly accumulated at a tumor tissue part, thus effects in acidic cytoplasm and between cytoplasm and cell nuclei with high reducibility are achieved, and therefore the amphiphilic block copolymer as a drug carrier has a good application prospect in preparing antineoplastic drugs.

The present invention provides a hydrazone bond-containing block copolymer having targeting antitumor activity. The preparation method comprises that: 4-nitrophenol methacrylate is subjected to RAFT polymerization to form a hydrophobic block, a good-biocompatibility hydrophilic polymer N-(2-hydroxypropyl)methacrylamide is introduced as a hydrophilic block, a double bond-containing folic acid targeting monomer is subjected to initiation polymerization to obtain a block polymer, and finally hydrazinolysis and a series of modification reactions are performed to introduce a pH sensitive group hydrazone bond. According to the present invention, with the doxorubicin-supporting block copolymer drug micelles, the toxicity of the small molecule drug in the body is reduced, and the residence time of the anticancer drug in the tumor cells is substantially prolonged; and the tumor cell growth inhibition experiment results prove that the copolymer provides a strong inhibition effect on HELA cells, the acidic pH-sensitive smart release bond (hydrazone bond) can identify the tumor cell micro-acidic environment, and the drug can break after reaching the tumor site so as to achieve the targeting antitumor activity of the drug, such that the copolymer is the antitumor activity substance having application prospects.

The invention discloses a Prussian blue-loaded targeting nanocomposite. The Prussian blue-loaded targeting nanocomposite comprises a PEGylated folic acid targeting lactic acid/glycolic acid copolymer shell coating Prussian blue nanoparticles, wherein paclitaxel is distributed on the PEGylated folic acid targeting lactic acid/glycolic acid copolymer shell. The objective of the invention is to provide the Prussian blue-loaded targeting nanocomposite capable of realizing photoacoustic/magnetic resonance multi-mode imaging for implementation of image-guided treatment, comprehensive treatment of tumors and improvement of tumor treatment effect, and a preparation method thereof.

The invention relates to a folate-conjugated-and-targeted nanocomposite particle, and a preparation method and application thereof. The nanocomposite particle uses polystyrene as a core and chitosan as a shell; the external surface of the shell is coated with Au nanoparticles and Fe3O4 nanoparticles, grafted with a targeting reagent folate and loaded with a photo-thermal reagent indocyanine green; and the nanocomposite particle is used as an infrared photo-thermal reagent, a drug carrier, a CT imaging contrast agent, a magnetic resonance imaging contrast agent or a fluorescence imaging contrast agent. Compared with the prior art, the invention has the advantage that the folate-conjugated-and-targeted nanocomposite particle prepared in the invention has good application prospects in CT imaging, magnetic resonance imaging, fluorescence imaging and photo-thermal treatment, can realize targeted delivery of the photo-thermal reagent to a tumor site, effectively kills cancer cells while reducing toxic and side effect on normal tissue and cells, further improves treatment effect and has great potential in promotion of accurate diagnosis and improvement of photo-thermal treatment (PTT) effect on cancers.

The invention discloses a polyphosphoester-based folate-targeted acid-sensitive core-crosslinked drug-loaded micelle and a preparation method thereof. The preparation method comprises the following steps: firstly, preparing an amphiphilic polyphosphoester segmented copolymer in a ring opening manner by adopting a one-pot method; modifying the terminal hydroxyl of the segmented copolymer to obtain a folate-modified segmented copolymer; then, modifying the hydroxyl on tetraglycol into a molecule of which the terminal contains aldehyde acetal group and azide group; and finally, preparing the acid sensitive core-crosslinked drug-loaded micelle by adopting a 'CuAAC' click reaction. The core-crosslinked micelle prepared by the method is capable of entrapping hydrophobic anticancer drugs by means of self-assembly and releasing the entrapped drugs because the broken aldehyde acetal group causes damage of the micelle structure under an acid condition, and can be used as a controlled drug release carrier. The core-crosslinked micelle disclosed by the invention can be used as an effective controlled release drug carrier, and has an excellent application value in the field of biomaterials and biomedicine.

The invention relates to a preparation method of a drug delivery system of an invisible thermosensitive liposome as well as an application of the drug delivery system of the invisible thermosensitive liposome in tumor treatment drugs, and can be used for effectively solving the problems that an existing tumor treatment drug is large in side effect, poor in treatment effect, and the like. The drug delivery system of the invisible thermosensitive liposome is composed of a thermosensitive liposome-loaded targeted heat sensitizing agent and chemotherapy drugs in a weight ratio of 1:3, wherein the invisible thermosensitive liposome is obtained through synthesis of carboxylic nanotubes, synthesis of folate-targeted carbon nano tube-lysine, preparation of the invisible thermosensitive liposome or synthesis of carboxylic nanotubes, synthesis of carbon nano tubes loaded with chemotherapy drugs, and preparation of the thermosensitive liposome. The preparation method disclosed by the invention is good in physical and chemical stability, simple and practicable in preparation condition, rich in material resources, low in cost, small in side effect and capable of effectively restraining multiplication of tumor cells, so that the effect of tumor-targeted treatment is achieved, and therefore, the preparation method is an innovation of a drug carrier in tumor-targeted treatment.

A composition for administration of a therapeutic compound to a multi-drug resistant cell in a person suffering from a drug-resistant cancer is described. The composition is composed of a carrier molecule and a folate targeting ligand, which is covalently attached to the carrier, and the therapeutic compound. In one preferred embodiment, the carrier is a liposome having a surface coating of hydrophilic polymer chains where a folate ligand is attached to the free distal end of at least a portion of the hydrophilic polymer chains, and the therapeutic agent is entrapped in the liposomes. The composition is effective to achieve accumulation of the therapeutic compound in the cell in an amount sufficient to be cytotoxic. Also described are methods for administering a therapeutic compound to a person suffering from a multi-drug resistant condition.

The invention relates to an epigallocatechin gallate-loaded folate-targeted carrier, which is prepared from zeolite imidazole skeleton, epigallocatechin gallate embedded in the zeolite imidazole skeleton, and folic acid-polyethylene glycol modified on the zeolite imidazole skeleton by means of an amido bond. The invention also relates to a preparation method and application of the epigallocatechingallate-loaded folate-targeted carrier. The folate-targeted carrier enhances the antioxidant effect of the epigallocatechin gallate, not only solves the problem of low utilization rate of the tea polyphenol epigallocatechin gallate, but also reduces the toxic and side effects of cancer treatment, and enables medical therapy to have targeting ability.

The invention discloses a folic acid targeted modified co-loaded doxorubicin hydrochloride and gambogic acid nanostructure lipid carrier preparation. In the embodiment, the preparation is prepared from 0.01 to 1 part of doxorubicin hydrochloride, 0.01 to 1 part of gambogic acid, 0.01 to 2 parts of phospholipid-polyethylene glycol-folic acid, 0.1 to 10 parts of solid lipid, 0.1 to 5 parts of liquidlipid, 0.1 to 3 parts of a lipid-soluble emulsifier and 1 to 10 parts of a water-soluble emulsifier. The invention further discloses a preparation method of the preparation. The nano preparation prepared by the method has the advantages of smaller particle size, even distribution, good stability and higher encapsulation efficiency; furthermore, the nano preparation improves water insolubility ofgambogic acid, prolongs drug residence time and has better active targeting; two drugs synergistically play curative effects, so that antineoplastic activity is enhanced, chemotherapeutic medicine dosage is reduced, and bioavailability is improved; meanwhile, multidrug resistance generated by the doxorubicin hydrochloride is inverted.

The invention relates to a preparation method of a nano delivery system between targeted redox-sensitive co-load chemotherapeutic drugs and P-gp resistance reversal agents. The redox-sensitive amphiphilic copolymers PCL7500-ss-PEG7500-ss-PCL7500 is utilized to build redox-sensitive polymer vesicle, intermolecular hydrophobic force is used to load hydrophobic taxol and Tarigquidar, adriamycin is loaded inside the hydrophilic chamber of the polymer vesicle via pH gradient method, folate targeting group is decorated on the surface of the polymer vesicle via covalent bond, thereby the polymer vesicle with synergistic activity with targeting, reduction and response and chemotherapy is built. P-glycoprotein(P-gp) of small molecules inhibitor Tariguidar reduces the drug resistance of drug resistance cells by blocking the efflux function of P-gp to the base drug, the picking up of drugs of drug resistance cells is increased, thereby the multiple drug resistance is reversed. The nano delivery system is capable of loading hydrophobic drugs and hydrophilic drugs, tumor targeting and having reducing and response to the tumor micro environment and realizing killing tumors by reserving the multiple drug resistance.

The invention discloses a polymer which is folate-polyoxyethylene-polypropylene oxide-polyoxyethylene-polycaprolactone (FA-F127-PCL) containing a folate-targeted group and an amphiphilic block taking polyoxyethylene-propylene oxide-ethylene oxide as a hydrophilic segment and polycaprolactone as a hydrophobic segment and having a novel chemical structure and a preparation method of the compound. The compound is good in slow-release effect.

The invention discloses a folic acid targeted magnetic functionalized molybdenum disulfide medicine carrier and a preparation method thereof. The preparation method comprises the following steps: firstly, by using a chemical co-precipitation method, modifying surfaces of molybdenum disulfide nano-sheets with MFe2O4 (M=Fe, Co and Ni) magnetic nano-particles, further performing amino-functionalized modification on the magnetic molybdenum disulfide nano-sheets, performing targeting modification by using folic acid as a targeting biological molecule through reaction that amido bonds are formed from carboxyl and amino, and finally loading an anti-tumor medicine, thereby obtaining the folic acid targeted magnetic functionalized molybdenum disulfide medicine carrier. The folic acid targeted magnetic functionalized molybdenum disulfide medicine carrier has the advantages of being controllable in operation process, gentle in reaction condition and easy in large-scale production; by adopting the preparation method, the medicine carrying capacity, blood half life and average retention time of the anti-tumor medicine are remarkably increased; and meanwhile, a medicine transmission system based on the nano composite material can reach and be enriched at focal parts in a targeted manner, and the medicine can be slowly released and is intelligently controllable, thereby achieving the purposes that the toxic or side effects of the anti-tumor medicines are alleviated, the medicine concentration at diseased regions is increased and the treatment effect on tumors is improved.

The invention discloses a preparation method of copper porphyrin-folate liposome nanoparticles and application thereof as a sound-sensitive agent. The preparation method comprises the following steps:dissolving copper porphyrin with methanol, dissolving lecithin and folate liposome in chloroform, mixing the two solutions, preparing a lipid film by a rotary evaporation method, and carrying out ultrasonic hydration with ultrapure water to synthesize the copper porphyrin-folate liposome nanoparticles. The nanoparticles have excellent targeting property in tumor cells with high expression of folate receptors, and are beneficial to enrichment at tumor sites so as to improve the anti-tumor effect; and under ultrasonic excitation, the copper porphyrin absorbs sound energy to generate transitionand converts surrounding oxygen into singlet oxygen to kill tumor cells. The invention provides the sound-sensitive agent capable of generating singlet oxygen through ultrasonic excitation to kill thetumor cells, and the folate targeted liposome is used as a carrier to carry the sound-sensitive agent, so that the water solubility and the targeting property are improved, and the sonodynamic therapy (SDT) effect is further improved.

The invention relates to a preparation method of a radionuclide 131I-labeled folic acid targeted multifunctional dendrimer. The preparation method comprises the following steps: (1) adding EDC and an NH2-PEG-COOH solution to folic acid for reacting so as to obtain FA-PEG-COOH; (2) adding HPAO to a dendrimer solution for reacting so as to obtain G5.NH2-HPAO; (3) adding EDC to the FA-PEG-COOH solution, activating, and adding to the G5.NH2-HPAO water solution for reacting so as to obtain dendrimer solution; and (4) adding N(C2H5)3 and acetic anhydride to the solution for reacting so as to obtain a functionalized dendrimer solution, and then adding Na131I for carrying out a labeling reaction so as to obtain the multifunctional dendrimer. The material prepared by the invention has excellent SPECT imaging and radioactive therapy functions, and the material has a potential application value in the field of forming a nano material integrating diagnosis and treatment.

A fluorescent targeting nanomaterial and a preparation method thereof. The preparation method is: use the polymer as the carrier of nanomaterials, and carry out azide modification on it, and then use the click chemical reaction to couple the targeting molecule folic acid and fluorescent tracer compounds to the polymer chain to obtain the fluorescent targeting coupling substances, and then ultrasonically dispersed to obtain stable targeted fluorescent nanomaterials. The targeted fluorescent nanomaterial obtained in the present invention is evenly distributed and can effectively reach the tumor site. Through the tracer effect of the fluorescent compound, the targeting effect and the occurrence of lesions can be intuitively and conveniently investigated during the experiment and detection process. The invention has the advantages that: the preparation method is simple; the fluorescent nano system is stable; the targeting molecule folic acid can improve the targeting of the fluorescent material.