52results about How to "Achieving Synergistic Therapy" patented technology

The invention discloses a pH-responsive polyethylene glycol-anticarcinogen conjugate, and a synthetic method and application thereof. After anticarcinogen molecules and polyethylene glycol are covalently linked through pH-sensitive phenylimide linkage, the conjugate is formed, wherein, anticarcinogen can be doxorubicin, epirubicin, daunorubicin, demethoxydaunorubicin or hydrochlorides of the above-mentioned anticarcinogens. The phenylimide linkage is stable under the condition of a normal physiological pH value but undergoes hydrolysis under the condition of a slightly acidic pH value, e.g., a solid tumor cell external pH value and a cell endosome and lysosome pH value; that is, the phenylimide linkage is sensitive to changes of pH values in a range of 7.4 to 4.5 or to below 4.5. The polyethylene glycol-anticarcinogen conjugate has amphiphilic nature and can form nanometer-scale micelle in a saline solution through self-assembly; the micelle can be used as a drug carrier to carry hydrophobic drugs and form a nanometer micelle preparation cladded with drugs, thereby realizing synergy therapy of a plurality of drugs.

The invention provides a genetically engineered cell membrane nano vesicle and preparation and an application thereof. The nano vesicle is composed of biological cell membranes, and the surface is transferred with a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a programmed death receptor 1 (PD-1), and internal entrapment catalase (CAT). TRAIL can specifically induce tumor celldeath, release tumor antigens and "dangerous signal molecules", and triggers an immune response; the PD-1 can combines PD-L1 protein on cancer cells, and blocks related immunosuppressive pathways; andthe CAT can catalyze H2O2 of a tumor site to produce oxygen, improves a tumor hypoxic environment, and enhances infiltration of immune cells. Through organic integration of the functions, effective elimination of tumor cells and rapid activation of an autoimmune system are achieved, and a multi-point synergistic anti-tumor effect is exerted.

The invention relates to a Prussian blue-based intelligent pH-triggered MRI drug release-monitoring synergetic nanometer diagnosis and treatment agent and a preparation method thereof. The nanometer diagnosis and treatment agent comprises hollow Prussian blue nanometer particles with mesopores. The surfaces of the hollow Prussian blue nanometer particles with mesopores are coated with KxMny[Fe(CN)6]z, wherein x is greater than or equal to 0.05 and less than or equal to 0.3, y is greater than or equal to 0.5 and less than or equal to 0.98 and z is equal to 1. The nanometer diagnosis and treatment agent comprises hollow mesoporous nanometer particles with core-shell structures. The HMPB-Mn nanometer diagnosis and treatment agent is used for tumor part pH-sensitive MRI and pH-sensitive drug release control in chemotherapy. Through combination with thermotherapy, MRI-guided thermotherapy-chemotherapy combined treatment on tumors is realized.

The invention relates to a preparation method and application of a glucose-oxidase-modified mesoporous manganese dioxide composition, and effectively solves the problem of providing new drugs for treating tumor diseases by preparing a glucose-oxidase-modified mesoporous manganese dioxide composition so as to realize synergistic inhibition of tumor cell growth by sonodynamic therapy and starvationtherapy. The preparation method of the glucose-oxidase-modified mesoporous manganese dioxide composition comprises the following steps: modifying surfaces of mesoporous manganese dioxide particles with glucose oxidase through amide bond reaction; physically loading a small-molecular sound sensitizer in pore canals of the mesoporous manganese dioxide, thereby obtaining an internally loaded sensitizer; and then, performing covalent modification on the outer side of the internally loaded sensitizer with glucose-oxidase-modified pharmaceutical composition of mesoporous manganese dioxide nanoparticles. Particle sizes of the glucose-oxidase-modified pharmaceutical composition of the mesoporous manganese dioxide nanoparticles are 100-300 nm; and mass ratio of the glucose oxidase to the manganesedioxide is 1 to 5. The preparation method of the glucose-oxidase-modified mesoporous manganese dioxide composition disclosed by the invention is stable, reliable, and low in cost; and moreover, the glucose-oxidase-modified mesoporous manganese dioxide composition can be used as a magnetic resonance imaging contrast agent for performing real-time monitoring on tumors. Therefore, the glucose-oxidase-modified mesoporous manganese dioxide composition is an innovation in tumor treatment drugs.

The invention relates to preparation and applications for double-response bi-crosslinked injectable hydrogel used for fine-controlled release of insulin. A chitosan derivative having excellent biocompatibility, biodegradability and antibacterial property is employed as a basic high molecule, and two dynamic bonds comprising imine bond and phenylboronate are employed for preparing pH/glucose bi-sensitive injectable hydrogel, and meanwhile bio-active molecules, such as glucose oxidase and the like, are introduced into the gel substrate through a disulfide bond and the like dynamic bonds to form a double glucose response system. Through the two glucose response factors, phenylboronate and the glucose oxidase, the concentration change of glucose in external environment can be sensed at the same time, thereby causing reversible reaction of the imine bond and phenylboronate in the system, so that the bi-crosslinked network structure of the hydrogel is changed greatly to release the medicines. High sensitivity and quick response to concentration change of glucose are achieved through double sensing units (the glucose oxidase and the phenylboronic acid group) and double accepting units (the imine and phenylboronate).

The invention relates to a macrophage tumor targeting therapy system combining a photothermal therapy effect and photo-thermally responsive biotherapeutic factor release and preparation and application thereof. The unique spatial and temporal selectivity of the macrophage tumor targeting therapy system can direct at a variety of solid malignant tumors, combines tumor photo-thermal therapy with biological therapy to achieve the local targeted comprehensive treatment of the tumors and reduce the toxic and side effects of traditional treatment caused by an off-target effect. The macrophage targeting tumor system can effectively inhibit the tumor growth of mice and prolong the survival time of the tumor-bearing mice, is an excellent tumor-targeting biological preparation and has great clinicalconversion application prospects.

The invention discloses a method for preparing camptothecin prodrug supramolecular hydrogel for drug combination. The method comprises adding alpha-CD and a water-soluble anticancer drug into an aqueous solution of a camptothecin prodrug to obtain a mixed solution, carrying out ultrasonic dispersion, and then carrying out standing so that the mixed solution undergoes self-assembly crosslinking through camptothecin prodrug hydrophobic polymerization and alpha-CD-PEG chain-based subject-object action to form supramolecular hydrogel. Through different loading methods of two drugs and reducing substances inside and outside tumor cells, two drugs with different hydrophobicity and anti-cancer mechanisms can be loaded, can be released at different time points in different zones in multiple stagesto be used in anti-tumor combined drug, and can realize coordinated treatment with drugs and inhibit tumors. The supramolecular hydrogel can be degraded, has good biocompatibility, is injectable, canbe implanted into a lesion site by injection, prevents the pain and tediousness of the surgical implantation and is favorable for damaged site irregular filling.

The invention discloses a nano diagnosis and treatment agent as well as a preparation method and an application thereof. The nano diagnosis and treatment agent is formed by self-assembling organic ligand molecules, Fe <2+> and amphiphilic molecules, wherein a structural formula of the organic ligand molecule is shown in the specification,-R is-CH3 or-CH2CH3, the novel organic ligand molecule designed by the invention can keep the stable valence state of Fe <2+>, Fe <2+> is delivered to a tumor site through a nano self-assembly technology, and a chemical kinetic treatment effect is generated. In addition, the organic ligand molecules also have near-infrared photothermal conversion capability, so that the photothermal therapy is realized, and meanwhile, the chemodynamic therapy effect is improved. The novel drug delivery mode provides a new strategy for tumor synergistic treatment.

The invention provides an amphiphilic conjugated oligomer, preparation thereof and drug-loaded nanoparticles prepared by self-assembly of the amphiphilic conjugated oligomer. The structural general formula of the amphiphilic conjugated oligomer is shown as a formula I in the specification. The conjugated oligomer has amphipathy and a self-assembly effect, the absorption spectrum undergoes red shift after the conjugated oligomer forms nanoparticles, and the conjugated oligomer has a stronger photothermal effect. By modifying a hydrophilic side chain group, a water-soluble nano material with a photo-thermal effect can be self-assembled by utilizing a hydrophobic effect, a hydrophobic small molecular drug is loaded and photo-thermal release is carried out, and the nano material has a very wide application prospect in the field of biomedicine.

The invention relates to a multifunctional Cu3BiS3-PEG-(Ce6-Gd<3+>)-FA nano composite material, and a preparation method and application thereof. The preparation method comprises the following steps: preparing oil-soluble Cu3BiS3 nanoparticles by using as Bi(DEDC)3 and Cu(DEDC)2 precursors, sequentially preparing DSPE-PEG/DSPE-PEG-NH2-modified water-soluble Cu3BiS3 nanoparticles, a Cu3BiS3-PEG-Ce6 water solution and a Cu3BiS3-PEG-(Ce6-Gd<3+>) water solution, and finally, coupling FA to the Cu3BiS3-PEG-(Ce6-Gd<3+>) to prepare the multifunctional Cu3BiS3-PEG-(Ce6-Gd<3+>)-FA nano composite material. The composite material is used for preparing CT (computerized tomography) contrast agents, MRI (magnatic resonance imaging) contrast agents, photothermal converters or photosensitive drugs. Compared with the prior art, the composite material can integrate photothermal and photodynamic treatment means to implement photothermal/photodynamic synergic treatment on cancers, and can also be used as MRI and CT contrast agents to implement bimodal imaging. The research on multiple molecule image probes on one molecule indicates that the composite material has wide application prospects in the field of biomedicine.

The invention relates to a functional nanodiamond medicine carrying system with targeting performance and a preparation method thereof. The characteristics of large specific surface area and high adsorbability of nanodiamond are used, so that hydrophobic anticancer medicine and photothermal materials are adsorbed onto the surface of the nanodiamond; proteins with antitumor activity are adsorbed onto the surface of the nanodiamond by using the physical action of mutual attraction of positive and negative charges, so that the dispersibility of nanometer particles in water is improved; and a targeting material coats the outer layer, and the photothermal materials are added into the inner layer, so that the effects of improving the medicine carrying capacity, delivering hydrophobic anticancermedicine to tumor positions in a targeted way and reinforcing the treatment effect of the medicine on the tumor by combining photothermal therapy are achieved. By using a simple and feasible method, the problem of burst release of the hydrophobic anticancer medicine is solved; and the active targeting problem of the nanometer particles is also solved.

The invention discloses a targeted drug composition for co-loading amphotericin B and adriamycin and an application of the targeted drug composition, and belongs to the fields of medicines and pharmaceutics, and provides a novel medical composition for treating leishmaniasis. Two medicines of amphotericin B and adriamycin having fluorescent tracing properties are used and loaded in a pharmaceutical carrier material which is favorable in biological safety and has pH responsiveness to form the medical composition, wherein the carrier material consists of hydrophilicity mannose residues which actively target macrophages, beta-cyclodextrin and hydrophobic propionyl. The medical composition is good in biological safety (cytotoxicity and hemolytic activity), and the stability, pH response medicine release properties, target capacity, and treatment efficiency are verified in a cell model. Besides, the synergistic reaction of the amphotericin B and the adriamycin is realized, so that the consumption of the medicine is greatly reduced, the side effect is reduced, the economic burden of patients is alleviated, and the targeted drug composition is hopeful to exert great effects on clinical application.

The invention relates to a preparation method of a gold nanorod-based engineering nano gel, wherein the method comprises the steps: with a gold nanorod as an inorganic core, modifying the surface of the gold nanorod with carboxyl groups by mercaptohyaluronic acid and activating; then grafting with acid phosphatase, adding a small molecular gel factor, making the property of the small molecular gelfactor changed from hydrophilcity to hydrophobicity by the enzyme digestion effect of the acid phosphatase, and self-assembling on the surface of the gold nanorod to form nano gel; and finally, loading the nano gel with chloroperoxidase, and thus obtaining the gold nanorod-based engineering nano gel. Compared with the prior art, the gelling method is simple and high in efficiency, both the gelling thickness and speed are adjustable, and the method applied in photothermal-enzyme combined therapy has mild and high-efficiency characteristics.

The invention relates to a preparation method of a medicinal reagent for treating colon cancer. The preparation method comprises the following steps: dissolving bovine serum albumin in deionized waterto prepare a uniform bovine serum albumin solution; adding an aqueous solution of a soluble trivalent iron salt into the bovine serum albumin solution under a stirring condition to obtain a bovine serum albumin-Fe solution; adding an ellagic acid solution into the bovine serum albumin-Fe solution under a stirring condition to prepare an ellagic acid-Fe-bovine serum albumin solution; and ultrafiltering and centrifuging the ellagic acid-Fe-bovine serum albumin (BSA) solution for purification to obtain an ellagic acid-Fe-BSA nanoparticle solution which is the medicinal reagent for treating coloncancer. Compared with the prior art, the medicinal reagent provided by the invention has a good treatment effect on colon cancer and can be used for enhancing chemical kinetics-photothermal therapy-chemotherapy combined treatment.

The invention relates to a preparation method, product and application of a silk fibroin-based thixotropic hydrogel, and belongs to the technical field of materials. A silk fibroin film is prepared, then immersed in water, and subjected to centrifugal treatment to discard undissolved silk fibroin film, and a hydrophilic silk fibroin extracting solution is obtained and left to stand. According to the preparation method, a natural silk is used as a raw material to prepare a thixotropic hydrogel, biosecurity is obtained, excellent thixotropic properties and viscoelasticity are obtained at the same time, pH, GSH, ROS, and NIR infrared light wave stimuli responsiveness are obtained, an anti-tumor drug is prepare by mixing the thixotropic hydrogel with one or more of an antitumor functional drugor a photosensitizer, and the antitumor drug has long-term retention and controllable drug release properties at the tumor site, the perfect combination of the stimuli responsiveness of the thixotropic hydrogel and photothermal therapy and photodynamic therapy can be realized, and the synergistic treatment of chemotherapy, photothermal, photodynamic is realized; and the thixotropic hydrogel is simple in preparation process, wide in source of raw materials, and low in cost, and the thixotropic hydrogel is suitable for expanding production.

The invention provides a polyphenol nano-reactor and a preparation method and application thereof. The polyphenol nano-reactor is prepared by comprising the following steps that enzyme is coated with an MOF structure to form nano-particles, a TA-PEI shell is formed on the surfaces of the nano-particles, the MOF structure is etched, and finally doxorubicin hydrochloride is absorbed on the surface of the TA-PEI shell. According to the polyphenol nano-reactor, a hollow structure is formed by etching the MOF template, so that the enzyme activity can be maintained; the TA-PEI cross-linked shell is used for protecting enzyme, so that complex environments such as pancreatin can be resisted; and the synergistic treatment of hunger treatment and chemotherapy is realized.

The invention discloses a preparation method of a mesoporous silica complex with drug controlled release and imaging functions. The preparation method comprises the following steps of (1) preparing anAu/Fe3O4@mSiO2-SH molecular probe; firstly, preparing Au nanoparticles; secondly, preparing Au/Fe3O4 nano particles with a shell-core structure; then, preparing Au/Fe3O4@mSiO2-SH nanoparticles by applying a reversed-phase microemulsion method; (2) preparing Au/Fe3O4@mSiO2/DOX-SS-PEG-HA; adding Au/Fe3O4@mSiO2-SH nanoparticles into a DOX ethanol solution, performing dispersing of the obtained nanoparticles into a DMSO aqueous solution, and adding SH-PEG-NH2, so as to obtain nanoparticles Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2; enabling HA to be dissolved in an MES solution through a carbodiimide method,enabling EDC and NHS to be added to serve as coupling agents, and enabling Au/Fe3O4@mSiO2/DOX-SS-PEG-NH2 to be added. The nanoprobe has three imaging functions of MRI, MPI and PAI and chemotherapy and photo-thermal treatment functions, can realize comprehensive, sensitive and targeted imaging of tumors, can perform real-time quantitative in-vivo monitoring of drug curative effects, and opens up abrand new field for accurate diagnosis and treatment of tumors at the molecular level.

The invention discloses preparation and application of a photo-response nitric oxide delivery/photo-thermal synergistic material, and firstly relates to a multifunctional nitric oxide donor molecule which has a structure shown as a formula I. The nitric oxide donor molecule provided by the invention and an amphiphilic polymer are jointly dissolved in an organic solvent; stable nano particles, namely the polymer assembly, are obtained through co-assembly in a nano flash precipitation mode, nitric oxide can be controllably released under white light irradiation, the stability of nitric oxide is improved, meanwhile, an efficient photo-thermal effect is achieved under 808 nm laser, and collaborative treatment is achieved.

The invention provides conjugated polymer and aggregation-induced emission micromolecule co-doped nano particles and a production method and application thereof. The conjugated polymer and aggregation-induced emission micromolecule co-doped nano particles are produced from the following raw materials through a nanoprecipitation method: a polymer of a structure shown in a formula I as shown in thedescription, a polymer of a structure shown in a formula II as shown in the description, and a compound of a structure shown in a formula III as shown in the description. Compared with existing anti-microbial technologies, the provided nano particles (DDNPs) formed by co-doping a conjugated polymer and aggregation-induced emission micromolecules have the advantages that photothermal therapy collaborates with photodynamic therapy, wherein a hydrophobic conjugated polymer DPPT-TT with strong near-infrared light absorption and high photothermal conversion efficiency and aggregation-induced emission micromolecules DPATP-CN with photodynamic activity are combined together through the nanoprecipitation method to produce the nano particles (DDNPs), and the nano particles (DDNPs) have efficient and stable photothermal performance and excellent ROS generating capability at the same time, so that synergistic therapy of photothermal therapy and photodynamic therapy is achieved; and the DDNPs havebroad-spectrum anti-microbial activity.

The invention provides an acid-responsive hyperbranched poly-prodrug nano-micelle as well as a preparation method and application thereof. The preparation method comprises the following steps: firstly linking a hydrophobic drug with an organic compound through an acid-sensitive acetal bond, and then synthesizing the amphiphilic hyperbranched poly-prodrug nano-micelle with acid responsiveness through a two-step reversible addition fragmentation transfer (RAFT) polymerization reaction. The acid-responsive hyperbranched poly-prodrug nano-micelle disclosed by the invention is simple in preparation process and has the advantages of being good in stability, prolonging the blood circulation time and improving the bioavailability of the drug. In addition, the nano-micelle can be broken in a low-pH environment in an inflammation or tumor microenvironment, a hydrophobic drug is rapidly released, and disease development is inhibited. The acid-responsive hyperbranched poly-prodrug nano-micelle disclosed by the invention provides a new choice for treating inflammatory diseases and tumors.

The invention discloses a nano compound for sonodynamic therapy with low skin phototoxicity, which is characterized in that disulfide bond-containing imidazole derivatives are used as organic ligands, metal ions are used as chelating metals, the disulfide bond-containing imidazole derivatives and the chelating metals form a nano metal organic framework, a sound-sensitive agent is entrapped on the nano metal organic framework, poloxamer is further coated on the outer layer of the metal organic framework, and the nano compound is prepared. The invention also discloses a preparation method. The nano-composite can reduce the phototoxicity of the sonosensitizer in normal tissues and organs, can realize intracellular rapid release through huge concentration difference of GSH inside and outside tumor cells, and has a molecular targeting effect and a sonodynamic curative effect.