50 results about "Integrin Receptor" patented technology

The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

The invention provides a symmetrical difunctional coupling agent compound (I), i.e. N-fluorenylmethyloxycarbonyl-L-beta-glutamate-di-N-succinimide (Fmoc-beta-Glu(OSu)-OSu), and a production method thereof. Based on the compound, a series of novel coupling compounds which respectively contain a symmetrical difunctional coupling base, i.e. beta-Glu (beta-glutamate) are prepared through being coupled to ligand molecules; the structural formula of the series of coupling compounds is shown as (II), wherein M1 is a -NH2-contained ligand of a target molecule T1, M2 is a -NH2-contained ligand of a target molecule T2, L is a linking group, and S is a report signal group. The compound (1) provided by the invention has been used in coupling a targeted integrin alphavbeta3 receptor ligands, gastrin-releasing peptide receptor ligands, telomerase inhibitor pharmacophores and epidermal growth factor receptor ligands, and thus, a plurality of coupled bi-ligand molecular imaging agents and coupled tri-ligand molecular imaging agents are synthesized. The invention further relates to the use of the compound (I) and the series of novel coupling compounds (II) in the preparation of imaging agent drugs.

The present invention is based on the discovery that a vascular stent or other implantable medical device can be coated with a biodegradable biocompatible polymer to which is attached a bioligand that specifically captures progenitors of endothelial cells (PECs) from the circulating blood to promote endogenous formation of healthy endothelium in Type II diabetics. In one embodiment, the bioligand is a peptide that specifically binds to an integrin receptor on PECs. The invention also provides methods for using such vascular stents and other implantable devices to promote vascular healing in Type II diabetics, for example following mechanical intervention.

The invention provides a serial cell-penetrating peptide modified tumor targeted and tumor penetrated nano drug delivery system capable of simultaneously identifying an integrin receptor and a transmembrane protein receptor, wherein the serial cell-penetrating peptide is mainly formed by connecting a DGR polypeptide fragment covalently at the C-tail end of polyarginine of the cell-penetrating peptide. The polypeptide not only can selectively identify two highly expressed receptors on the surfaces of the tumor cells, but also can be efficiently mediated into the cells. The nano drug delivery system mainly consists of a nano carrier, a drug and a lipid-polyethylene glycol-serial cell-penetrating peptide ligand interstitial compound and is a potential tumor targeted treatment carrier.

The invention discloses a USPIO-PLA-RGD compound, a preparation method and application thereof. The USPIO-PLA-RGD compound uses USPIO as a core, is coated by PLA outside, and is labeled as PLA-USPIO; and the USPIO-PLA-GRD compound obtained through covalently coupling carboxyl of a functional group exposed on the surface of PLA and amidogen of RGD peptide has a hydrated grain diameter of between 90 and 105 nm. The USPIO-PLA-RGD compound can be applied as magnetic resonance tumor angiogenesis targeting contrast agent. The invention realizes targeting developing by the characteristics of high affinity of an alpha v beta3 integrin receptor and ligand RGD peptide thereof, and the combination has the characteristics of high specificity, selectivity, saturation and affinity, clear biological effect and the like. The concentration of a medicament in a partial focus can be increased, and toxic and side effects can be reduced by using the ligand RGD peptide as a vector of USPIO through the mediation effect of the receptor, so that the aim of development of a targeting tumor angiogenesis living body is realized.

The present invention is directed to an antibody or derivative thereof of human origin for inhibiting platelet aggregation, characterized in that it is effective by substantially exclusive binding to the activated state of platelet integrin receptor GPIIb/IIIa.

The invention relates to a preparation method of SPECT/CT (Single Photon Emission Computed Tomography/Computed Tomography) dual-mode imaging contrast agent based on a second-generation polyamide-amine dendritic polymer. The method comprises the following steps: by taking the second-generation polyamide-amine dendritic polymer as a template material, sequentially modifying a radionuclide 99mTc chelating agent NOTA and a pegylated RGD (Arginine-Glycin-Aspartate) molecule on the surface; coating gold nanoparticles through an in-situ reduction synthesis method; and finally, labeling the radionuclide 99mTc, thereby obtaining the product. The SPECT/CT contrast agent prepared by the method disclosed by the invention has excellent colloidal stability, excellent biocompatibility, long blood circulation time and excellent in-vitro/vitro SPECT/CT imaging effect, has a specific targeting effect on C6 cells of an alphavbeta3 integrin receptor on the cell membrane surface and provides a good thought for developing a novel dual-mode nano contrast agent.

Techniques for the production of flow-oriented collagen gels using hydrodynamics to influence the assembly of collagen fibers. Highly concentrated monomeric solutions of collagen are subjected to shear and extensional flow as they are drawn onto a substrate to induce fibrillogenesis under a high Ph buffer. The produced gel captures the flow induced ordering of molecular collagen upon fibril formation. The depositing or the induction of fibrillogenosis occurs without the application of a magnetic field to the concentration of collagen. These highly oriented 3D scaffolds are capable inducing contact guidance and guiding mammalian cell growth. The collagen fibers mimic the construction of in vivo fibers with the characteristic D-periodicity and the integrin receptors on the fibroblasts respond to this organization. The industrial applications of three-dimensional collagen gels as a biomaterial are widespread from drug delivery to burn repair or tissue engineering system.

An immunoliposome composition targeted to the alpha-V-integrin subunit of integrin receptors comprised of ligand-targeted liposomes bearing at least one targeting-ligand derived from an antibody and having binding specificity for at least one integrin receptor comprising an alpha-V subunit including αvβ1, αvβ3 αvβ5, αvβ6, or αvβ8 integrin cell receptors is described. The antibody-derived targeting ligand may be a Fab′ fragment, a scFv, or a the like. Binding of the immunoliposome to αv-integrin expressing cells, preferably results in internalization of the immunoliposome for cytoplasmic delivery of a liposome-entrapped agent.

The invention discloses a preparation method of a near-infrared fluorescent compound which accurately targets tumor cells and is activated by beta-galactosidase, wherein the structure of the fluorescent compound is shown in a formula I. The probe compound combines a substrate alphaD-galactose (alphaD-gal) recognized by beta-galactosidase with cyanine near-infrared fluorophores to introduce an alphavbeta3-integrin receptor-targeted ligand c-RGD. The ability of the ligand c-RGD targeting tumor cells is utilized for near-infrared imaging of live mouse tumors overexpressing beta-galactosidase. Theprobe has the advantages that receptor-mediated cell uptake and molecular target activation are combined to realize real-time and non-invasive detection of beta-galactosidase in living tissues. The probe can be successfully applied to improve cancer imaging and promote effective cancer diagnosis.

The invention discloses amino cyanine fluorescent dyes connected with cyclopeptide [cyclo(RGD)] and a preparation method therefor and application thereof. The structural formula of the compounds is shown in I. The compounds consist of structural units III and III; the structural unit II is a derived cyanine dye structure which is water soluble fluorescent molecules, the spectrum of which has relatively great Stokes shift, and the molecules have relatively less toxicity to normal cells; the structural unit III is a cyclopeptide structure of a specific ligand of an alpha v beta 3 integrin receptor and can be used for targeted orientation. The fluorescent dyes have the double function characteristic of tumor imaging diagnosis and targeted therapy.

The invention belongs to the technical field of biological medicines and relates to an integrin receptor-targeted taxol nanocomposite and a preparation method and application thereof. The preparation method comprises the following steps of: synthetizing a terminal carboxyl group-modified amphiphilic block copolymer HOOC-polyethylene glycol-poly trimethylene carbonate (HOOC-PEG-PTMC); connecting the amphiphilic block copolymer with a carboxyl group by an arginine-glycine-aspartic acid (RGD) polypeptide through an amido bond to obtain an RGD peptide-modified amphiphilic block copolymer; and introducing fat-soluble antitumor drug taxol into the amphiphilic block copolymer to prepare the integrin receptor-targeted taxol nanocomposite. Proved by an experimental result, the taxol nanocomposite can be used for increasing the drug concentration of the antitumor drug at a target part, reducing the accumulation of the antitumor drug at a non-target part and effectively increasing the treatment index of the drug. Shown by the result of an antitumor pharmacodynamic experiment, compared with a taxol control group, the taxol nanocomposite is more excellent in antitumor activity.

α_vβ₃ Integrin receptor targeting liposomes comprise a cationic amphiphile such as a cationic lipid, a neutral lipid, and a targeting lipid. The targeting lipid includes a non-peptidic α_vβ₃ integrin antagonist.

The invention discloses an RGD/PTX-coated ZIF-90 drug delivery system and a preparation method thereof, and belongs to the field of biological medicine. According to the drug delivery system, on the basis of the metal organic framework ZIF-90, aldehyde groups and amino groups of RGD are connected through a Schiff base reaction, PTX is entrapped through the adsorption effect, no extra chemical reagent is introduced in the whole process, and the drug delivery system is safer and more environmentally friendly. The preparation method is simple, the ZIF-90 and the RGD are stirred to obtain RGD/ZIF-90, then the RGD/ZIF-90 and the PTX are stirred together, and the RGD/PTX ZIF-90 composite material is obtained. According to the drug delivery system, aiming at the physiological characteristics of specific high expression of an alpha v beta 3 integrin receptor and low pH of tumor cells, RGD can target the tumor cells, and when the RGD reaches the vicinity of the tumor cells, the skeleton of ZIF-90 collapses, so that PTX is intensively released near the tumor cells, the anti-tumor activity is improved, the side effect of the drug can be reduced, and the drug delivery system has the advantages of strong anti-tumor effect, few side effects and high stability.

The invention provides a novel polypeptide which not only can be actively targeted to highly expressed integrin receptor of tumor cells, but also can efficiently mediate cell entry. The novel polypeptide TR(c(RGDfK)-AGYLLGHINLHHLAHL(Aib)HHIL-Cys) is formed by connecting cyclic RGD peptide (c(RGDfK)) of specificity-targeted integrin receptor and non-specific pH sensitive cell penetrating peptide TH(AGYLLGHINLHHLAHL(Aib)HHIL-Cys) through covalent bonds. The novel polypeptide TR is modified onto the surface of a drug carrier system, and can mediate the drug carrier system to more efficiently deliver to the inside of the tumor, so that the tumor can be more effectively treated.

The invention discloses a multifunctional targeting gene vector as well as a preparation method and application. The multifunctional targeting gene vector is a polymer represented by P(LA-co-GA)-PEI-PEG-NLS-G-TAT-G-REDV; the multifunctional targeting gene vector disclosed by the invention has a membrane penetration function, a nuclear location function, and a targeting function on endothelial cells; cell extraction of a gene compound prepared from a multifunctional targeting polypeptide modified gene vector is improved through specific recognition of REDV peptide and an integrin receptor on the surfaces of the endothelial cells and the membrane penetration effect of TAT. The nuclear internalization of the gene is promoted through a mutual effect of a nuclear localization signal NLS and a nuclear membrane, so that a gene delivery effect is improved and the aims of improving the transfection efficiency and promoting cell migration and proliferation are realized. The problem of non-viralvectors at present is solved.

The invention relates to the technical field of pharmaceutical preparations, in particular to a composite exosome loaded with polypeptide and a small-molecule antitumor drug as well as a preparation method and application of the composite exosome. According to the composite exosome drug delivery system, exosome (Exosome, EXO) derived from human umbilical cord mesenchymal stem cells is used as a carrier, annular polypeptide cRGD is embedded on the membrane surface of the carrier so as to be delivered to melanoma cells with high expression of alpha v beta 3 integrin receptors in a targeted mode, small-molecule anti-tumor drugs are entrapped in the exosome membrane, and the drug delivery efficiency is improved. And constructing a composite exosome drug delivery system cRGD-EXO/small molecule antitumor drug. In-vivo and in-vitro experiments show that the drug delivery system has good tumor targeting property, and shows a remarkable tumor inhibition effect while reducing the toxic and side effects of the drug. The invention provides a small molecule drug delivery system which is good in targeting property, high in biological safety and exact in tumor inhibition effect for tumor treatment with high expression of an alpha v beta 3 integrin receptor.

The invention discloses a small-particle-size drug-loaded micelle for actively targeting alpha v beta 3 integrin receptor high-expression tumor cells and a preparation method of the small-particle-size drug-loaded micelle. The micelle comprises drug-loaded micelles, the surface of the drug-loaded micelle is modified by an alpha v beta 3 integrin receptor high-affinity ligand overexpressed on the surface of a tumor cell, aiming at the defects of insufficient targeting property and the like of antitumor drugs, a small-particle-size drug delivery system (the average particle size is about 15 nm)capable of targeting the high-expression tumor cells of the alpha v beta 3 integrin receptor is designed and constructed, PDI (0.2) is used for achieving the purposes that a medicine actively targetsspecific tumor cells and can be rapidly and effectively taken by the cells, the medicine effect of the medicine is brought into play to a greater extent, and the distribution of the medicine in the whole body and toxic and side effects caused by the distribution are reduced.

The present invention provides brain cells, such as normal brain cells, apolipoprotein E deficient brain cells, or apoE4 containing brain cells, that are treated with a compound which can modulate integrins and/or integrin receptors to produce increased sequestration of and/or accumulation of and/or uptake of Aβ, and/or changes in cathepsin D content and/or lysosomal dysfunction, and/or microglia activation in the brain cells. The present invention also provides methods for producing such cells and methods for using the cells for screening an agent or substance that modulates the sequestration of and/or accumulation of and/or uptake of Aβ, and/or lysosomal dysfunction, and/or changes in cathepsin D content and/or microglia activation in the brain cells. The method further provides a new therapeutic target, antagonism of glutamate receptors, for the treatment of neurodegenerative diseases which are characterized by inter alia, abnormal amyloid uptake and/or accumulation.