48 results about "Dual targeting" patented technology

This disclosure features structurally-stabilized and / or cysteine-reactive peptide inhibitors for selective targeting of BFL-1, or dual targeting of BFL-1 and MCL-1. Also disclosed are methods of using such structurally-stabilized and cysteine-reactive peptides in the treatment of BFL-1- and / or MCL-1-expressing or -dependent cancers or diseases of cellular excess (e.g., autoimmune or inflammatory conditions). Also provided are combination therapies comprising such structurally-stabilized and / or cysteine-reactive peptides and inhibitors of the DNA damage response pathway, such as an ATM kinase inhibitor, ATR kinase inhibitor, CHK1 / 2 inhibitor, or PARP inhibitor; or an inhibitor of MCL-1, or a selective inhibitor of BCL-2, or an inhibitor of BCL-2 / BCL-XL, for the treatment of BFL-1-expressing or -dependent cancers (e.g., AML), BFL-1 and MCL-1-expressing or -dependent cancers, or diseases of cellular excess (e.g., autoimmune or inflammatory conditions).

This patent discloses a dual targeting lipid-based formulation designed for precise drug delivery to the thyroid gland, addressing the complexities of thyroid disorders. The formulation integrates two key technologies: the RGDFK Targeting Motif and Iodine Coupling. The RGDFK motif enhances specific binding to αvβ3 integrin receptors, facilitating internalization of therapeutic agents. Simultaneously, the Iodine Coupling technology leverages the thyroid gland's natural affinity for iodine, ensuring increased accumulation of lipid-based vesicles in thyroid tissue. Applications of this formulation extend to targeted treatment of diverse thyroid disorders, symptom-specific relief, and nutritional supplementation. The formulation serves as a fundamental component in pharmaceutical compositions, adaptable for various administration routes. The manufacturing process emphasizes scalability, reproducibility, and standardized quality. A comprehensive treatment kit has been devised, offering a convenient and tailored approach to thyroid drug delivery. In conclusion, this dual targeting lipid-based formulation signifies a paradigm shift in thyroid disorder therapeutics, promising precision, efficacy, and patient-centric care. As it advances towards clinical applications, it holds the potential to redefine the landscape of thyroid health management for enhanced patient outcomes.

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 application discloses a VEGF / TIE-2 double-targeting polypeptide and application thereof in preparation of an antitumor drug, and relates to the technical field of biological medicine.The VEGF / TIE-2 double-targeting polypeptide (named as RTP) provided by the application is composed of an amino acid sequence capable of target-recognizing VEGF and TIE-2, an amino acid sequence capable of self-assembling to form a beta-sheet nanofiber, an amino acid sequence capable of target-recognizing carbonic anhydrase IX and an enzyme-reactive amino acid sequence capable of being specifically cut by MMP-2.RTP can occur conformational change and self-assemble in tumor cells to form stable water-insoluble nanofibers, and can strongly inhibit tumor neovascularization and metastasis through the VEGF and TIE-2 double-signal pathways and inhibit the progress of the tumor.

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 invention discloses a nanoparticle targeting bone tissue macrophages, its preparation method, and its applications, belonging to the field of biomedical technology. This invention employs a dual targeting mechanism, modifying the nanoparticle surface with bone-like peptide sequences and mannose-modified ligands, enabling the nanoparticles to specifically recognize macrophages in the bone tissue environment. The bone tissue macrophage-targeting nanoparticle system prepared by this invention can significantly improve targeting efficiency, anti-inflammatory effects, and tissue repair effects, while reducing systemic side effects, providing a new treatment approach for bone injury repair and showing promising clinical application prospects.

The invention discloses a bionic photo-thermal nano motor for targeted regulation and control of a solid tumor matrix-immunosuppression microenvironment and a preparation method and application thereof, and belongs to the technical field of biomedical materials.The preparation method comprises the steps that polydopamine nanoparticles and a K2PtCl4 aqueous solution are subjected to condensation reflux, and asymmetric PDA-Pt is prepared; and preparing a cancer-related fibroblast and breast cancer cell fusion membrane and coating the surface of PDA-Pt with the cancer-related fibroblast and breast cancer cell fusion membrane. The nano-motor realizes dual targeting of matrix cells and tumor cells through a surface modified fusion cell membrane, targeted ablation CAFs regulates and controls a tumor matrix microenvironment, a good tumor permeation effect is realized by cooperating with H2O2 responsive self-driving of the nano-motor, a mild photo-thermal-catalytic synergistic effect is formed by a photo-thermal effect of PDA and peroxidase-like activity of Pt nano-enzyme, and a good tumor permeation effect is achieved. And finally, the tumor immunosuppression microenvironment is remarkably improved, and the tumor immunotherapy effect is improved.

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 invention provides an exosome oral soluble film with a multi-targeting function, which is prepared from the following components in parts by weight: 10 to 20 parts of active substances, 20 to 60 parts of carrier materials for wrapping exosomes or drug-loaded exosomes, 50 to 100 parts of film-forming agents, 20 to 40 parts of disintegrating agents, 10 to 25 parts of plasticizers, 1 to 5 parts of flavoring agents and 1 to 10 parts of antioxidants, wherein the active substance is an exosome or a drug-loaded exosome, and the carrier material is a polylactic acid-glycolic acid copolymer-sulfydryl group, polyethylene glycol and polyethylene glycol diacrylate. According to the scheme, the carrier material entrapped with the exosome has a dual targeting effect, so that the exosome or the exosome loaded with the medicine can accurately reach the ulceration position of the colonic mucosa, and accurate treatment is achieved; and the exosome is administrated in an oral dissolution manner, so that a patient can take the exosome with high compliance.

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.

The present invention discloses a diagnosis and treatment integrated material based on single-atom iron dual-targeting integrin and chemokine receptor, its preparation method and application, the composite material of the present invention is Fe-SA@DOX@TPGS- b ‑AA‑RGD / AMD3465, which is more stable in PBS, has a strong inhibitory effect on integrin α v The dual targeting of β3 and CXCR4 chemokine receptors allows it to be specifically delivered to the tumor site during blood circulation. In the acidic microenvironment of the tumor, it reacts with H2O2 to produce reactive oxygen species and release doxorubicin, achieving synergistic anti-tumor properties. 64 Cu is used to label the material and perform nuclear medicine positron emission tomography (PET) imaging to monitor the material's metabolic process in the body, the accumulation of various tissues, organs and tumors, and achieve the purpose of tumor diagnosis.

The invention discloses a PD-L1CPS automatic interpretation analysis model and an application of the PD-L1CPS automatic interpretation analysis model. The process of predicting the curative effect of the immunotherapy by the PD-L1CPS analysis model comprises the following steps: collecting tumor tissues of a patient suspected to be cancer according to an imaging detection result, preparing the tumor tissues into PD-L1 immunohistochemical staining pathological sections, and obtaining a full-section image WSI; using a PD-L1CPS automatic interpretation analysis model to extract plaque level classification module features, region segmentation module features and cell recognition module features, and calculating a CPS score value; and comparing the CPS score value with a model reference value, and giving a prediction result of the malignant tumor patient on the immunotherapy curative effect. According to the method, the tumor region is doubly positioned through the plaque classification model and the region segmentation model, the interference of morphological fuzziness is avoided, the performance and the processing efficiency are improved, and the generalization ability of the PD-L1CPS automatic interpretation analysis model is verified by using two batches of external queues.

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 invention belongs to the technical field of biological drugs. Provided are a chimeric antigen receptor targeting CD19 and CD22, and a CAR-T cell and the use thereof. The chimeric antigen receptor targeting CD19 and CD22 is obtained by means of concatenating elements including a CD8 signal peptide, a CD19scFv light chain variable region, a linker peptide, an anti-CD22 nanobody, a linker peptide, an anti-CD19scFv heavy chain variable region, CD8 extracellular and transmembrane regions, and 4-1BB and CD3ζ cytoplasmic regions. A T cell expressing the chimeric antigen receptor targeting CD19 and CD22 is capable of simultaneously targeting CD19 and CD22 antigens. This dual targeting can not only broaden the scope of tumor cell killing, but can also enhance the anti-tumor activity, providing a new means for treating B-cell malignancies and / or B-cell-related autoimmune diseases.

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 belongs to the technical field of drug carriers, and particularly relates to an ROS-responsive dual-targeting drug nano-carrier CD38-PHD / G-NP as well as a preparation method and application of the ROS-responsive dual-targeting drug nano-carrier CD38-PHD / G-NP. The dual-targeting drug nano-carrier CD38-PHD / G-NP disclosed by the invention is co-loaded with GSI and sustained-release dihydroartemisinin (DHA), and a CD38 antibody is modified. The CD38 antibody recognizes T-ALL cells, and the GSI specifically targets Notch1, so that dual targeting is realized. The double-strategy CD38-PHD / G-NPs can realize controlled release of drugs in T-ALL, repair the cytotoxicity of GSI and induce greater ferroptosis, and solves the side effects of gastrointestinal tracts through the CD38 antibody, thereby providing a new view angle for targeted therapy of T-ALL patients.