33 results about "Dual targeting" patented technology

The invention relates to the technical field of bioengineering, in particular to a targeting nanoparticle for treating acute respiratory distress syndrome as well as a preparation method and application of the targeting nanoparticle. Comprising the following steps: (1) combining MP peptide with DSPE-PEG2000-MAL through a maleimide-mercaptan reaction, dialyzing the obtained conjugate, washing, and freeze-drying, so as to obtain a DSPE-PEG2000-MP conjugate; and (2) mixing the conjugate, lipid, a pharmaceutical preparation and a solvent, removing the solvent to obtain a lipid film, hydrating the lipid film, and performing membrane extrusion to obtain the nanoparticles. The invention not only provides a novel efficient and safe ARDS treatment scheme, but also provides an innovative mode for the design of a nano-drug delivery system based on cell mediation. And due to the dual targeting capability, excellent anti-inflammatory efficiency and good biocompatibility, the nano-material has a wide prospect in clinical application.

The present application provides a polypeptide or a pharmaceutically acceptable salt thereof, wherein the polypeptide has an amino acid sequence as shown in SEQ ID NO: 1. The polypeptide or the pharmaceutically acceptable salt thereof can bind to PD-1 and CTLA-4, and is used for effectively inhibiting PD-1 and CTLA-4. Thus, the polypeptide or the pharmaceutically acceptable salt thereof can be used for detecting PD-1 and / or CTLA-4, and can also be used for treating or preventing diseases mediated by PD-1 and / or CTLA-4 (such as tumors or cancers, for example, lung cancer, melanoma, lymphoma, leukemia and other diseases involving tumor immune escape).

The invention provides a Motixazotide-nitrogen mustard conjugate and a preparation method and application of a fluorescent probe of the Motixazotide-nitrogen mustard conjugate, and belongs to the field of polypeptide preparation and biological medicine. According to the present invention, a solid phase polypeptide synthesis method is adopted to covalently link a DNA alkylation reagent nitrogen mustard and a CXCR4 targeting peptide Motixazotide, and further couple with a fluorescent dye so as to successfully prepare a series of novel conjugates and fluorescent probes thereof; experiments prove that the Motixazotide-nitrogen mustard conjugate and the fluorescent probe thereof prepared by the invention can be used for remarkably improving the anti-tumor activity of nitrogen mustard and the targeting property of the nitrogen mustard to tumor cells. Meanwhile, the rhodamine B labeled dinitrogen mustard conjugate BCCR has a specific targeting effect on a CXCR4 receptor and a dual targeting effect on a tumor cell nucleus. The conjugate realizes real-time tracing of the whole process of tumor targeting, cell delivery and nuclear localization, and provides a powerful tool for curative effect evaluation and mechanism research, so that the conjugate has good clinical transformation prospect and application value.

The application discloses a kind of dual targeting / drug-loaded reduction-sensitive nano-carrier, and the micelle is formed by the micelle of block polymer by solvent evaporation method, and the multi-block polymer is Tel-PEG-ss-PCL, the hydrophilic end of which is PEG with targeting group Tel, and the hydrophobic end is PCL, which is a core-shell structure, the core is the hydrophobic end PCL, and the shell is the hydrophilic block with targeting group Tel.The nano-carrier selects the polymer micelle with hydrophilic end polyethylene glycol and hydrophobic end polycaprolactone as drug carrier to improve the problem of poor water solubility of drug;Tel, an angiotensin II type receptor (AT1R) ligand, is used to simultaneously target CAFs and tumor cells overexpressing AT1R, kill tumor cells and CAFs, and double drug loading to overcome drug resistance;Meanwhile, disulfide bond is used to respond to high concentration glutathione (GSH) in tumor cells to achieve precise control release of drug in cells.The nano-carrier realizes the treatment effect of solubilization of poorly soluble drug, tumor and CAFs dual targeting and reversal of drug resistance.

This application relates to the field of biomedical technology, and more specifically to the compound represented by formula (I), its pharmaceutically acceptable salt, its deuterated compound, its stereoisomer, its tautomer, or mixtures thereof, and the use of said compound as an immunomodulator for dual targeting of IKZF1 and IKZF3. TIFF2026511128000306.tif30170

The invention discloses a composite water-soluble vaccine adjuvant and a preparation method thereof, and belongs to the technical field of biological medicines. The adjuvant is based on a composite technology of a water-soluble component and a targeted delivery carrier, through a dual targeting effect of mannose modified beta-glucan, the uptake efficiency of dendritic cells on antigens is remarkably improved, and regulation and control on immune response are realized in cooperation with levamisole. The adjuvant has the characteristics of uniform particle size, excellent water solubility, good storage stability and the like, the immunological enhancement effect of the adjuvant is remarkably superior to that of a traditional adjuvant, and the adjuvant can be widely applied to research and development of vaccines for influenza, tuberculosis, tumor and the like, and has important clinical value and industrialization potential.

This invention discloses a dual-targeting DNA vaccine delivery system based on calcium phosphate lipid nanoparticles, belonging to the field of biomedicine. The delivery system comprises calcium phosphate containing histone H1 and an HPV E6 / E7 fusion gene plasmid, and a lipid bilayer membrane of DSPE-PEG-2000-Mannose. This system achieves targeted uptake by dendritic cells through mannose modification and relies on histone H1-mediated DNA nuclear transport. The dual targeting significantly enhances antigen expression efficiency. In vitro and in vivo experiments have demonstrated that this delivery system exhibits good biocompatibility and high stability, effectively activating antigen-specific T-cell immune responses, and possesses both HPV infection prevention and cervical cancer treatment effects, providing a new strategy for cervical cancer prevention and treatment.

This invention relates to the field of drug delivery systems, and discloses a nanoparticle for photodynamic therapy and its preparation method. The nanoparticle has a core-shell-corona composite structure, comprising, from the inside out: a core layer composed of NaYF4 upconversion nanoparticles; a middle layer: a mesoporous Zr-MOF layer; a shell layer: a pH-responsive polymer layer formed by linking folic acid to polyethylene glycol-polycaprolactone block copolymer via hydrazone bonds; and a targeting corona layer comprising dual targeting ligands, namely a bicyclic [6.1.0]nonyne-functionalized iRGD peptide and an azide-functionalized anti-EGFR nanobody 7D12. The nanoparticles of this invention possess advantages such as high stability, strong targeting, and high photosensitizer loading, and can efficiently generate reactive oxygen species.

The invention provides synthesis and application of a tetravalent platinum prodrug with a mitochondrial GLS / mt-DNA dual-targeting function. According to the invention, oxaliplatin-resistant liver cancer cell mitochondria is taken as a target spot, tetravalent platinum is taken as a skeleton template, a double-drug multifunctional tetravalent platinum prodrug (LND-Pt-TPP) capable of co-targeting mitochondria GLS1 and mt-DNA is synthesized, and liver cancer treatment sensitivity of oxaliplatin is restored by intervening drug-resistant cell glutamine metabolism and avoiding DNA damage repair. The pharmaceutical composition is used for treating oxaliplatin-resistant liver cancer. The invention further studies the action mechanism that the tetravalent platinum prodrug (LND-Pt-TPP) with the mitochondrial GLS / mt-DNA dual-targeting function intervenes in GLS1 mediated glutamine metabolism to increase the formation of an mt-DNA-Pt compound, and has very important clinical application value.

The present invention introduces a novel immunotherapeutic approach utilizing dual-targeting cancer cell therapy. This therapy involves dual -targeting constructs that co-express either chimeric antigen receptors (CARs) alone or a CAR with a bispecific T-cell engagers (BiTEs) to target two distinct antigens. This innovative design minimizes antigen escape and enhances cytotoxic efficacy by harnessing the advantages of both CAR-T cells and BiTEs. Additionally, the invention discloses the use of bidirectional or in-line promoters to co-regulate the expression of dual CARs or co-expression of a CAR and a BiTE. It also provides polynucleotide and amino acid sequences for these dual -targeting CAR constructs, with or without BiTEs, for the treatment of B-cell malignancies, autoimmune disorders, and other B cell-related diseases.

The application discloses a kind of composite water-soluble vaccine adjuvant and preparation method thereof, belong to biological medicine technical field.The adjuvant is based on the composite technology of water-soluble component and targeted delivery carrier, through the dual targeting effect of mannose modified beta-glucan, the uptake efficiency of dendritic cells to antigen is significantly improved, and the regulation of immune response is realized by synergistic levamisole.The adjuvant has the characteristics of uniform particle size, excellent water solubility, good storage stability, etc., and the immune enhancement effect is significantly better than traditional adjuvant, and can be widely used in the research and development of influenza, tuberculosis and tumor vaccines, has important clinical value and industrialization potential.

The invention belongs to the technical field of biological pharmacy, and particularly discloses an LAG-3 and PD-L1 dual-targeting polypeptide and application thereof. The polypeptide P3E-D7 with high affinity to LAG-3 and PD-L1 is obtained through phage display peptide library screening and polypeptide structure optimization, the affinity of the polypeptide to LAG-3 and PD-L1 is high, and binding of LAG-3 / MHC-II and PD-1 / PD-L1 can be effectively blocked. The polypeptide coupled drug BsPep-IMDQ is obtained by coupling the polypeptide P3E-D7 and the imidazoquinoline IMDQ micromolecule drug, the toxic and side effects of the micromolecule drug can be effectively inhibited, polarization of M2 macrophages is inhibited, and activation of T cells is promoted, so that the growth of tumors is remarkably inhibited, and the polypeptide coupled drug has no obvious toxic and side effects and is suitable for clinical application. And a basis is provided for research and development of medicines for resisting tumors or other types of diseases.

The invention discloses a 2-(2-phenethyl) chromone compound with COX-2 and 5-LOX dual-targeting inhibitory activity as well as a preparation method and application of the 2-(2-phenethyl) chromone compound, and belongs to the technical field of natural pharmaceutical chemistry. According to the compound, 2-(2-phenethyl) chromone is taken as a skeleton, and a functional group capable of being specifically combined with COX-2 and 5-LOX enzymes is introduced through chemical modification, so that double-target synergistic inhibition on two inflammatory mediators is realized. The invention also provides a synthesis method of the compound, which comprises the following steps: selecting high-purity 2-(2-phenethyl) chromone as an initial raw material, carrying out structural modification under the action of a catalyst, introducing key functional groups such as acrolein and acrylic acid into specific positions of a chromone ring, synthesizing a target compound through a multi-step reaction, and carrying out purification treatment on a reaction product. An in-vitro experiment result shows that IC50 (half maximal inhibitory concentration) of COX-2 is 1.12 [mu] M, and IC50 of 5-LOX is 1.18 [mu] M; and an acute toxicity experiment LD50 is greater than 2000mg / kg.

The application discloses a CD7 and CD3 double-targeting fusion protein and application thereof. Specifically, the application discloses an isolated fusion protein, which comprises, from N-terminal to C-terminal, (a) an anti-CD7 single-domain antibody (CD7 VHH); (b) an anti-CD3 single-domain antibody (CD3 VHH); and (c) a transmembrane region, which is used for anchoring the fusion protein on a cell membrane or a viral envelope. And a T cell-targeting pseudotyped lentiviral vector based on the fusion protein is constructed. The pseudotyped lentiviral vector of the application can effectively target and activate T cells, and can deliver the expression CAR-containing vector into T cells, thereby effectively activating T cells and enhancing the target killing ability of T cells.

Disclosed herein are methods of using GLP-1R and GCGR dual targeting agonist Mazdutide or a pharmaceutically acceptable salt thereof in the treatment of subjects having both diabetes and obesity.

This invention provides a method for preparing and applying a class of Motixafortide-nitrogen mustard conjugates and their fluorescent probes, belonging to the fields of peptide preparation and biomedicine. This invention utilizes a solid-phase peptide synthesis method to covalently link the DNA alkylating agent nitrogen mustard with the CXCR4 targeting peptide Motixafortide, and further couple it with a fluorescent dye, successfully preparing a series of novel conjugates and their fluorescent probes. Experimental verification shows that the Motixafortide-nitrogen mustard conjugates and their fluorescent probes prepared in this invention can significantly enhance the antitumor activity and targeting of nitrogen mustard to tumor cells. Simultaneously, the rhodamine B-labeled dinitrogen mustard conjugate BCCR exhibits specific targeting of the CXCR4 receptor and dual targeting of the tumor cell nucleus. These conjugates enable real-time tracking of the entire process of tumor targeting, cell delivery, and nuclear localization, providing a powerful tool for efficacy evaluation and mechanism research, thus possessing promising clinical translational prospects and application value.

Disclosed herein are methods of using GLP-1R and GCGR dual targeting agonist Mazdutide or a pharmaceutically acceptable salt thereof in the treatment of subjects having both diabetes and obesity.

The present application provides a kind of for human epidermal growth factor 2 (HER2) and integrin dual targeting binding protein and its production method and application.Integrin dual targeting binding protein includes HER2 specific nanobody or single chain antibody and integrin polypeptide ligand (RGD).Dual targeting antigen binding protein can target recognition HER2 and integrin protein specifically expressed on the surface of tumor cell, interfere with the expression and signal transduction of HER2 and integrin protein, while inhibiting the expression of EGFR, HER2, HER3, HER4, so as to maximum degree inhibit the growth signal pathway of tumor cell.The dual targeting binding protein can also be used as a drug carrier to deliver drugs directly to the tumor site.The dual targeting binding protein described in the present application can be prepared by E. coli expression system.

The invention belongs to the technical field of biomedical cosmetics, and discloses a double-target 5alpha-reductase and adiponectin receptor cyclic peptide as well as application and a preparation method thereof. The cyclic peptide is formed by cyclizing three amino acid units, namely arginine, phenylalanine and tyrosine through peptide bonds, and comprises pharmaceutically acceptable salts, solvates, stereoisomers or isotope labels of the cyclic peptide. The compound reduces generation of dihydrotestosterone by inhibiting 5alpha-reductase, activates an adiponectin receptor AdipoR pathway to promote energy metabolism and proliferation of hair papilla cells, and realizes double-target synergistic anti-alopecia. The invention also discloses application of the cyclopeptide in preparation of medicines or cosmetics for preventing or treating alopecia and a solid-phase synthesis preparation method. Through double-target synergistic interaction, the hair follicle cell proliferation rate can be remarkably increased at extremely low concentration, and the dosage is reduced compared with that of a traditional medicine; the composition is constructed by adopting physiological amino acid, has no systemic sex hormone side effect during local external use, and is high in safety.

The invention discloses a superparamagnetic nano drug delivery system with biological and magnetic dual targeting and tumor drug and magnetic and thermal dual tumor cell killing and application, and belongs to the technical field of biological medicine. The system is composed of a lipid component, a chemotherapeutic drug and surface carboxyl modified FeO nanoparticles, wherein the lipid component is prepared from cholesterol, DSPE-PEG2000 and folic acid modified DSPE-PEG2000. According to the drug loading system, efficient enrichment of tumor sites is achieved through folic acid receptor mediated biological targeting and physical targeting of an external magnetic field, and tumor cells are killed through chemotherapy drugs and a magnetocaloric effect in a synergistic mode. Experiments show that the encapsulation efficiency of the system on adriamycin reaches 80%, the drug release rate under the magnetocaloric condition is 50%-60%, and the system shows significant targeting and killing effects in tumor cells expressing folate receptors. The invention has the advantages of simple preparation process, strong targeting property, high killing efficiency, low toxic and side effects and the like, and is suitable for thermochemotherapy treatment of cancers.

The invention relates to the technical field of biological medicines, in particular to a responsive RNA (Ribonucleic Acid) delivery system for brain glioma as well as a preparation method and application of the responsive RNA delivery system. Through fusion of blood-brain barrier penetrating peptide ANG-2 mediated cross-blood-brain barrier delivery and combination of Siglec-15 mediated immune targeting recognition, a dual targeting mechanism is constructed, a delivery system can be guided to accurately recognize a glioma focus, the enrichment amount of the delivery system in a focus area is remarkably increased, a foundation is laid for playing a role of a nucleic acid drug, and the application prospect is broad. The targeting and effectiveness of treatment are effectively improved, and damage to normal brain tissues is avoided. A dual stimulation release mechanism of acid response and active oxygen response can accurately respond to glioma focuses and endogenous stimulation in cells. Through the synergistic compatibility of the G0-C14 carrier and the charge reversal polylysine, the loading efficiency of the YTHDF2 siRNA is effectively improved, and meanwhile, the cycling stability of the nucleic acid medicine in vivo is enhanced.

This invention relates to the field of drug delivery system preparation technology, and specifically provides a drug delivery system, its preparation method, and its applications. The drug delivery system of this invention includes a carrier, and a targeting peptide and an aptamer connected to the carrier. The drug delivery system obtained by modifying the carrier with the targeting peptide and aptamer has dual targeting properties, enabling more accurate targeted drug delivery through a dual targeting mechanism.

The application discloses a pH-responsive deformable double-targeting nano-protein and a preparation method and application thereof, and the method comprises the following steps: after carboxylated mannose is activated through an EDC / NHS system, the carboxylated mannose is reacted with an albumin solution, and mannose-modified albumin is obtained through dialysis purification; the mannose-modified albumin is mixed with an inhibitor IRG1-IN-1, and IRG1-IN-1 is loaded through hydrophobic interaction to obtain mannose albumin nanoparticles; ferritin is used as a carrier, and oxaliplatin is loaded through a solvent displacement method to obtain ferritin nanoparticles; CHO-PEG2k-CHO is used as a connecting agent, and the mannose albumin nanoparticles and the ferritin nanoparticles are crosslinked through a Schiff base reaction to form large-size pH-responsive double-targeting nano-proteins. The double-targeting separable characteristics of the nano-proteins can realize specific treatment, kill tumor cells, interfere with immune cell metabolism, block metabolic immunosuppression, and promote anti-tumor immunotherapy.

This invention belongs to the field of biomedicine and relates to a lipid component for generating Her2-targeting chimeric antigen receptor neutrophils in vivo, its preparation method, and its application in the treatment of solid tumors. The lipid nanoparticles are dual-targeting lipid nanoparticles, with the dual targeting achieved through a Ly6G antibody fragment and a NEBP peptide. The lipid nanoparticles contain a lipid component and mRNA encoding Her2-CAR and IFN-γ. This invention uses lipid nanoparticles (LNPs) to deliver the mRNA encoding Her2-CAR and IFN-γ, delivering it in vivo to neutrophils to express Her2-CAR and IFN-γ, generating CAR-neutrophils. This eliminates the cumbersome steps of in vitro engineering of immune cells and avoids the potential adverse reactions caused by in vitro preparation and reinfusion of CAR-immune cells.

Provided are methods of using GLP-1R and GCGR dual targeting agonist mazdutide or a pharmaceutically acceptable salt thereof for the treatment of subjects having heart failure.

The invention belongs to the technical field of cancer treatment, and discloses application of co-targeting EZH2 / DNMT to synergistically reversing castration-resistant prostate cancer resistance. We prove that dual targeting of DNMT and EZH2 breaks epigenetic transformation, so that tumors are re-sensitive to androgen deprivation therapy. The strategy not only eliminates CRPC in a preclinical model, but also reverses immunosuppression, so that cytotoxic T cell infiltration is increased by 11.4 times. We data extend the use of EZH2 inhibitors beyond PRC2 dependent cancers, localizing the interaction of DNA methyltransferase with EZH2 as a targeting weakness in extracellular matrix rich solid tumors. The combination therapy provides a mandatory solution to overcome stromal disorders, which provides a revolutionary strategy for biomechanical factor driven malignancies.

The invention discloses an FAP-alpha and MMPs dual-targeting compound as well as a radiolabeled derivative and application thereof, and belongs to the crossing field of pharmaceutical chemistry and radiopharmaceutical chemistry. The compound has a structure as shown in a formula I, and can be simultaneously combined with FAP-alpha (IC50 is less than or equal to 10nM) and MMPs (such as MMP-9 IC50 is less than or equal to 20nM) in a tumor microenvironment with high affinity through modular design of a conjugate planar ring system and a specific amino acid chain (Y-Z). By replacing the effect group 3R with different radionuclides / chelating agents, the diagnosis and treatment integrated nuclide probe can be constructed. According to the double-targeting strategy, the residence time of the probe in tumors is obviously prolonged (2-10 times) compared with that of a single-targeting FAPI drug, and the target / non-target ratio is improved, so that the drug dosage and toxicity are reduced. The compound and the composition are suitable for diagnosis and treatment of FAP / MMP positive solid tumors (such as ovarian cancer and lung cancer) and fibrotic diseases.

The application discloses a pancreatic cancer JAK2 and STAT3 dual-target inhibitor containing a phenoxy acetic hydrazine compound and application thereof, and the dual-target inhibitor comprises a compound containing a phenoxy acetic hydrazine structure. The dual-target inhibitor comprises a pharmaceutically acceptable salt. The pancreatic cancer JAK2 and STAT3 dual-target inhibitor containing the phenoxy acetic hydrazine compound is applied to the preparation of a drug for treating pancreatic cancer. The drug has a new use in treating pancreatic cancer by inhibiting tumor proliferation, migration and invasion, angiogenesis, epithelial mesenchymal transition, blocking a cell cycle and promoting cell apoptosis. The pharmaceutical preparation of the drug composition comprises tablets, capsules, syrup, suspensions and injections. A drug for treating pancreatic cancer comprises the pancreatic cancer JAK2 and STAT3 dual-target inhibitor containing the phenoxy acetic hydrazine compound and a pharmaceutically acceptable carrier. The application has the beneficial effect that the pancreatic cancer JAK2 and STAT3 have a better inhibiting effect, the experimental results show that the inhibiting effect is good, the application prospect is wider, and the safety is better.

The invention relates to a nano-drug for dual-targeting M2 type macrophages as well as a preparation method and application of the nano-drug, and belongs to the technical field of biological medicines. The nano-drug for dual targeting of M2 type macrophages comprises USPIO, N-ADOBSA and CD163, the CD163 has the function of targeting M2 type macrophages, and the N-ADOBSA has the ability of targeting lysosome, so that the USPIO can act on the lysosome of M2 type macrophages in a targeting manner, the nano-drug is positioned to the lysosome, ferric iron in the USPIO is combined with a metabolic pathway of the lysosome, and the effect of targeting the M2 type macrophages is achieved. The ferroptosis process of the M2 macrophages is induced, so that the effects of targeting the M2 macrophages and reducing the activity of the M2 macrophages are realized, and the application significance in tumor treatment is important.

The invention provides a digestive tract tumor targeting composite nano material and a preparation method thereof, and belongs to the field of medical products. The method comprises the following steps: preparing a ferroferric oxide-loaded mesoporous silica core-shell structure, loading a chemotherapeutic drug and potassium permanganate, and performing in-situ reduction through ascorbic acid to obtain drug-loaded core-shell nanoparticles; coating the nanoparticles with eudragit S100 to form a pH response layer, and performing amination to prepare an intermediate product; the preparation method comprises the following steps: aminating aldehyde hyaluronic acid through ethanediamine, coupling with MMP-2 sensitive peptide and connecting with folic acid-N-hydroxysuccinimide ester in sequence to prepare folic acid modified enzyme response hyaluronic acid; and finally covalently grafting to the intermediate product to obtain the target composite nano material. The material has pH response enteric protection, MMP-2 enzyme triggered drug release and folic acid-hyaluronic acid dual-targeting functions, is suitable for targeted chemotherapy of gastrointestinal tumors, and can improve the curative effect of drugs and reduce toxic and side effects.