32results about How to "Enhanced EPR effect" patented technology

The invention provides a lipidosome-polymer drug-loaded nanoparticle and a preparation method and application thereof. The lipidosome-polymer drug-loaded nanoparticle comprises a three-layer structure, wherein the innermost layer is the drug-loaded nanoparticles formed by taking an amphiphilic cationic polymer as a carrier-coated chemotherapeutic drug; the intermediate layer is a platelet inhibitor layer adsorbed onto the surface of the drug-loaded nanoparticles; and the outermost layer is a lipid bilayer connected with tumor microenvironment responsiveness polypeptides. The lipidosome-polymer drug-loaded nanoparticle disclosed by the invention is capable of specifically targeting tumor tissues, has tumor microenvironment responsiveness, and can achieve the effects of improving tumor vascular permeability without influencing functions of blood vessels at normal tissue or cell parts, enhancing permeability and retention of the drug-loaded nanoparticles to tumor cells, enhancing the EPR effect, improving enrichment of the drug-loaded nanoparticles at tumor location and realizing high tumor killing efficiency.

The invention relates to a somatostatin receptor-mediated tumor targeted pharmaceutical composition which adopts a targeted somatostatin receptor functional polypeptide and polyethylene glycol for simultaneously modifying a pharmaceutical carrier, and an anti-tumor drug or/and an anti-angiogenic drug is delivered to the tumor part, thereby enhancing the tumor treatment effect.

The invention relates to a multi-function nano prodrug system based on a dendrimer, which belongs to the technical field of biomedicines and nano medical science. The nano system comprises four function parts: an outermost layer RGD (arginyl-glycocoll-aspartate) cyclic peptide as an active targeting head group (1), a polyethylene glycol (PEG) hydrophilic chain segment (2) connected with the targeting head group and the dendrimer, an anti-tumour drug (3) connected with the dendrimer by an acid sensitive chemical bond and a dendrimer kernel (4). The general formula of the nano system is RGD-PEG-Dendrimer-DOX (doxorubicine), wherein the macromolecule attribute of a dendrimer vector makes a vector system passively target to tumor tissues through an EPR (Enhanced Permeability and retention) effect; the RGD cyclic peptide makes the vector system actively target to the tumor tissues through the interaction of a ligand and a receptor and promotes the endocytosis of the tumor tissues; the acid sensitive chemical bond ensures that a drug-carrying system is stable in systemic circulation and releases active drugs after arriving tumor positions and entering an acid organelle to perform the function of cytotoxicity.

Disclosed herein are compounds and compositions including a polyglycerol nanocarrier, a therapeutic agent or imaging agent, and optionally a targeting agent. In certain aspects the disclosed compounds include biocompatible hyperbranched polymer nanocarriers. Such compounds and compositions are useful for the targeted delivery of antitumor agents and imaging agents to tumors in vivo. Methods are also disclosed for detecting and treating such tumors.

The invention discloses an adriamycin nano drug delivery system as well as a preparation method and application thereof. The drug delivery system comprises the following components in percentage by weight: 0.02%-1.5% of active ingredient containing adriamycin, 1%-20% of solid lipid, 0.1%-20% of liquid lipid, 0.5%-20% of emulsifier and 0.1%-5% of isoosmotic adjusting agent, wherein the solid lipid and the liquid lipid form nanoparticles to cover the active ingredient containing the adriamycin. The preparation method comprises the following steps: (1), uniformly dispersing the active ingredient containing the adriamycin, the solid lipid, the liquid lipid and fat-soluble emulsifier in an organic solvent, evaporating the organic solvent to obtain an oil phase; (2), uniformly dispersing other emulsifiers and the isoosmotic adjusting agent in water to obtain a water phase; (3), adding the water phase into the oil phase for emulsifying drop by drop; (4), homogenizing under high pressure; (5), cooling and degerming. The adriamycin nano drug delivery system disclosed by the invention can be used for realizing co-transporting of the adriamycin and a chemosensitizer, so that the killability of the adriamycin on liver cancer cells is strengthened.

The present invention provides a group of novel SMA derivatives and a covalent conjugate of the derivatives and an active substance. More specifically, the present invention provides: an SMA derivative which contains (i) a styrene-maleic acid copolymer (SMA) and (ii) a side chain (b) that contains a functional group (a) selected from among —NH2, —SH, —OH, —COOH, —NH—(C═NH)—NH₂ and —C(CH₂—OH)₃ and introduced into a carboxyl group of a maleic acid residue of the SMA via an amide bond or an ester bond, and wherein when a plurality of side chain (b) is introduced into the SMA, the side chains (b) may be identical or different from each other; and a conjugate of this SMA derivative and an active substance.

The invention relates to a preparation method of a pH value-sensitive curcumin-loading micelle (single chain) precursor. The chemical formula of the pH avid-sensitive curcumin micelle (single chain) precursor is MPEG-PLA-N=Cur. The preparation method comprises the following steps: dissolving modified methoxy poly(ethylene glycol)-poly(lactic acid) of which the terminal contains hydrazino and single-terminal phenolic hydroxyl carbonylated curcumin serving as reaction raw materials in a proper feeding ratio under the action of a certain solvent; carrying out a bonding reaction to form a pH avid-sensitive curcumin micelle monomer. Compared with the prior art, the preparation method has the advantages that a hydrazone bond is introduced into the conventional diblock copolymer (MPEG-PLA) structure and is bonded with curcumin which is a hydrophobic medicament, and a formed amphiphilic polymer is self-assembled into a micelle in an aqueous solution.

The invention relates to a photodynamic therapy system and a method of continuously generating singlet oxygen. The invention discloses multifunctional lanthanides nanoparticles, a preparing method thereof, a method of using the nanoparticles for generating singlet oxygen and the photodynamic therapy system. By combining a hyperbaric oxygen chamber, the lanthanides nanoparticles are excited by near infrared laser to achieve oxygen supply sensitization, so that targeted delivery of a nanoparticle drug and generation of singlet oxygen are promoted, and therefore the technical problems that in the prior art, singlet oxygen is generated insufficiently and the photodynamic therapy system is poor in effect are solved.

The present invention discloses multifunctional imaging cross-linked stable nanometer drug-loading micelles and a preparation method thereof. The preparation method comprises: adding 200 mg of an amphiphilic drug carrier mPEG-S-Trityl-Cys-Dopa and a hydrophobic anti-cancer drug to an organic solvent, dissolving, and carrying out dialysis by using a dialysis bag to remove free Fe<3+>; carrying out centrifugation, and filtering the supernatant by using a 0.45 [mu]m microporous filtration membrane; and carrying out freeze drying on the filtrate, wherein the freeze-dried product is the multifunctional imaging cross-linked stable nanometer drug-loading micelles mPEG-S-Trityl-Cys-Dopa-Fe<3+>/hydrophobic anti-cancer drug. According to the present invention, the obtained nanometer micelles have the stability and the pH-sensitivity, and can be visible by MRI, can break through the single-function mode of the traditional drug delivery system, can integrate the MRI imaging function and the drug carrier function, and can achieve the synchronous diagnosis and treatment of cancers.

The invention relates to an amorphous calcium carbonate composite nano-medicine with an effect of inducing ferroptosis of tumor cells and a preparation method of the amorphous calcium carbonate composite nano-medicine, and belongs to the technical field of medicines. After the composite nano-medicine enters the tumor cells, the degradation of nanoparticles is promoted by means of the acidic environment of lysosomes, meanwhile, the lysosomes are subjected to permeabilization to release doxorubicin and ferrous ions through the protonation of dendrimers, wherein ferrous ions can promote the conversion of polyunsaturated fatty acids of cell membranes to lipid peroxides and induce ferroptosis of the tumor cells, and DOX can promote oxidative stress to increase the content of hydrogen peroxide in the cells while inducing apoptosis, so that iron-dependent ferroptosis caused by lipid peroxidation induced by the ferrous irons is further enhanced. The composite nanoparticles can not only increase the therapeutic effect of tumors, but also reduce the side effects caused by chemotherapy.

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 present invention provides conjugates containing metal binding ligands, as well as nanocarriers prepared from the conjugates.

The invention provides a chemical exchange saturation transfer contrast agent as well as a preparation method and application thereof, and belongs to the technical field of nuclear magnetic resonanceimaging. The contrast agent is a novel LipoCEST contrast agent; on the basis of keeping the advantages of high sensitivity and the like of the original iodine CEST contrast agent, high biocompatibility and safety are realized; the defects of fast discharge in the tumor region, low retention rate and the like of a conventional CEST contrast agent such as iohexol can be overcome; the EPR effect of the tumor region is improved. The contrast agent is formed by coating an iodine contrast agent with a surfactant; the surfactant is one or a mixture of more of phosphatidylcholine liposomes, phosphatidyl ethanolamine liposomes, phosphatidylserine, lecithin or cholesterol. The contrast agent is used for nuclear magnetic resonance imaging.

The invention discloses a demethylcantharidate-loaded mesoporous silica nanoparticle. A preparation method of the demethylcantharidate-supported mesoporous silica nanoparticle comprises the steps of preparing ammonia-modified mesoporous silica through a co-precipitation method and preparing DM-NCTD@NH2-MSN by electrostatic adsorption loading of demethylcantharidate. The prepared DM-NCTD@NH2-MSN has obvious slow-release effects and long-acting tumor suppression effects, and has a better application prospect as a DM-NCTD tumor target delivery system.

The invention relates to a preparation method and application of an EPR effect enhanced combined pharmacy system, and can effectively solve the problem of preparation of anti-tumor drugs. The technical proposal comprises that a pharmaceutical adjuvant sodium alginate with good biocompatibility and easy gelation is used as a base material, Fe<3+> is used as a crosslinking agent and a door controlled switch, hydroxychloroquine and combretastatin are used as model drugs, combretastatin is used as a vascular target molecule, and a nano gel as an anti-tumor deliquite system is built. The preparation process is simple, stable and reliable, and has the advantages of energy saving and environmental protection. The prepared EPR effect enhanced combined pharmacy system can be efficiently accumulatedat a tumor target site and achieves long-term controlled release effect; under the stimulation of tumor microenvironment, the particle size can be transformed from big to small, and deep penetrationof tumors can be achieved; endogenous H2O2->.OH transformation can be activated and is used for local high-efficiency treatment of tumors. Anti-vascular and anti-autophagy combined pharmacy can play asynergistic and significant treatment effect and a new strategy is provided for improving the efficiency of tumor treatment.

The invention belongs to the technical field of biological medicines, and relates to a PM (PTXPEG-PLA micelles)-coated nano-cluster and a preparation method thereof. The preparation method comprises the following steps of using an emulsifying ultrasonic method to prepare prepared PM into the PM-coated nano-cluster through a crosslinking agent; finally, adding hydrophilic micromolecules with negative charges to neutralize surface positive charges, and improving the hydrophilic property of a system. The PM-coated nano-cluster has the advantage that the PM is coated into a hydrophobic kernel of the micelles, so that on the basis of not influencing the higher drug carrying amount of the original micelles, the particle size of the system is effectively increased, the hydrophilic property of the system is improved, the circulating time in a human body is prolonged, the tumor EPR (enhanced permeability and retention) effect is enhanced, and the validity and safety of the medicine in the clinical application are improved.