52 results about "Tumor targeting" patented technology

The invention belongs to the technical field of biological medicines, and discloses an engineered bacterium for in-situ expression of a microtubule inhibition protein in a tumor and application of the engineered bacterium. The engineering bacteria are formed by constructing microtubule inhibition protein genes to an expression vector and finally transferring the expression vector into bacteria. The engineering bacterium can be colonized in a tumor microenvironment in a targeted manner, expresses microtubule inhibition protein, effectively inhibits tumor cells and remarkably inhibits solid tumor growth, and is excellent in safety.

The application discloses a kind of R8 and Tf co-modified mebendazole liposome targeted preparation and its preparation method, application, belong to the field of biological medicine. In view of the poor solubility of mebendazole in water, difficult to penetrate blood-brain barrier, the problem of insufficient tumor targeting in brain glioma treatment, the application adopts film hydration-step modification process, and octaarginine (R8) and targeting ligand transferrin (Tf) are simultaneously modified on the surface of mebendazole-loaded liposome, and the preparation prepared by the application has an encapsulation efficiency of not less than 95%. The preparation can break through blood-brain barrier and precisely enrich in brain glioma lesions, and the in-vivo tumor inhibition rate is more than 90%, with low toxicity and side effects. The preparation can be used for preparing brain glioma therapeutic drugs, and provides a new drug for targeted treatment of brain glioma.

The application relates to the technical field of biological medicine, and discloses a targeted ferroptosis-inducing conjugate as well as a preparation method and application thereof. The structural formula of the conjugate is as follows: the conjugate contains a prostate cancer targeting peptide segment WHDGFK, and is connected with an iron death-inducing antibacterial peptide KRIVKWIIKLLR through a disulfide bond, so that the conjugate has tumor targeting and microenvironment response release functions, not only endows the antibacterial peptide KRIVKWIIKLLR with tumor selective delivery capacity, but also realizes specific release of the active peptide in target cells by reducing the disulfide bond by using high-concentration glutathione (GSH) in tumor cells, thereby synergistically enhancing the antitumor effect and reducing the systemic toxicity.

Disclosed are a modified nucleic acid aptamer-paclitaxel conjugate, a preparation method therefor, and use thereof. The modified nucleic acid aptamer-paclitaxel conjugate comprises paclitaxel, a succinic acid linker, and an AS1411 aptamer modified with a G4 ligand. In the modified nucleic acid aptamer-paclitaxel conjugate, a nucleic acid aptamer and paclitaxel are coupled by means of a linking bond, and then a target conjugate is obtained by modifying the structure of the nucleic acid aptamer with a G-quadruplex stabilizer using a chemical method. The conjugate has better tumor targeting properties and ultimately specifically targets tumor cell surface proteins, thereby exhibiting anti-cancer activity for the treatment of cancer.

This invention discloses a monoclonal antibody targeting NECTIN4, its associated nucleic acid, vector, host cell, and its application in the preparation of antitumor drugs, belonging to the field of biomedical technology. The monoclonal antibody comprises a specific heavy chain variable region VH and a light chain variable region VL. The HCDR1-3 amino acid sequences of VH are shown in SEQ ID NO:1-3, and the LCDR1-3 amino acid sequences of VL are shown in SEQ ID NO:4-6. This invention also provides the nucleic acid encoding the antibody (SEQ ID NO:10), a vector containing the nucleic acid, and a host cell containing the nucleic acid or the vector. This Nectin4 monoclonal antibody can specifically target and bind to the NECTIN4 protein on the surface of tumor cells, inhibiting tumor cell cycle progression, proliferation, migration, and invasion by regulating the NF-κB pathway. As a naked antibody, it exhibits significant tumor-targeting inhibitory effects, especially for esophageal cancer, and can also be used for targeted therapy of other malignant tumors such as breast cancer and lung cancer. This monoclonal antibody has a better safety profile than ADC drugs, providing a new option for tumor targeted therapy.

This invention discloses a near-infrared cyclic metallic iridium (III) photosensitizer and its synthesis method. The BDP-Ir prepared by the method of this invention can be used at low doses (IC50). 50 =68nM) at low power (10mW·cm) ‑2 It exhibits high photosensitivity under 808nm excitation, successfully solving the problem of sacrificing both excitation wavelength and photosensitivity efficiency; at the same time, its synergistic biomimetic artificial nano-hybrid delivery system can effectively enhance the tumor targeting and immune escape ability of photosensitizers.

The application discloses a kind of attenuated salmonella load adjuvant nano combination medicine, the combination medicine is modified to bacterial surface by means of amino and carboxyl condensation reaction, adamantane is simultaneously modified to adjuvant nano medicine surface using diselenium dynamic bond, then the host-guest interaction of adamantane and cyclodextrin is used to assemble two, and then nano medicine is stably combined on the surface of attenuated salmonella.Diselenium dynamic bond can be broken by ultrasound response, so as to realize the effect of drug release.This combination medicine has the tumor targeting enrichment ability of bacteria and the release characteristics of adjuvant nanoparticles under the action of ultrasonic wave, can realize targeted delivery and deep penetration in tumor tissue, and obtain significant tumor inhibition effect under ultrasonic stimulation.The experimental results show that the combination medicine exhibits good therapeutic effect in inhibiting tumor growth, and has excellent biological safety.

The present disclosure relates to conjugates of camptothecin analogs of the formula T-(L-D) m with a cell binding molecule. The present disclosure also provides methods for preparing conjugates of camptothecin analogs with cell binding agents, and methods of using the conjugates in tumor-targeted therapy.

The present disclosure relates to a composition of a biologically pure isolate of the genus Salmonella comprising archival strain CRC1674, wherein the isolate further comprises a disruption of at least one gene selected from the group consisting of aroA, rfaH, and thyA and a chemotherapy agent, an immunotherapy agent, an androgen receptor antagonist, or a combination thereof. The present disclosure also relates to the method of use of this composition in treating cancer, particularly prostate cancer and pancreatic cancer.

This invention relates to a biomimetic nanodelivery system ANG-2-CMLNPs. The preparation method of ANG-2-CMLNPs includes the following steps: Step 1: Prepare EZ NPs using a one-step self-assembly method, then co-incubate them with siRNA to obtain siRNA-EZ NPs; Step 2: Prepare liposomes using a thin-film hydration method, then modify them with ANG-2; Step 3: Add U87 MG cells to cold PBS, centrifuge to remove intact cells and debris, and the resulting precipitate is the glioma cell membrane fusion membrane; Step 4: Mix the Angiopep-2 modified liposomes obtained in Step 2 with the glioma cell membrane fusion membrane obtained in Step 3, and sonicate to obtain a composite; Step 5: Co-extrude the composite obtained in Step 4 with the siRNA-EZ NPs obtained in Step 1 to obtain the biomimetic nanodelivery system ANG-2-CMLNPs; In the above preparation process, when EZ... When the mass ratio of NPs to siRNA is 125:1 and the mass ratio of ANG-2 modified liposomes to CM is 1:5, the prepared ANG-2-CMLNPs delivery system achieves the optimal functional balance between the ability to cross the blood-brain barrier (BBB) ​​and tumor targeting efficacy.

The application discloses a novel radionuclide therapeutic drug targeting nucleolus DDX24 helicase and a preparation method and application thereof. 64 The Cu-DOTA-TDP-2 has good tumor targeting uptake specificity, and is expected to provide a precise molecular imaging method for esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has high radiochemical yield and specific activity, good chemical stability, high affinity for DDX24 helicase, and a simple and easy-to-operate preparation method, and can be used for the treatment of DDX24 high-expression malignant tumors; the novel radionuclide targeted drug 177 The Lu-DOTA-TDP-2 has excellent biological safety performance and good tumor inhibition effect in esophageal squamous cell carcinoma and other DDX24 high-expression malignant tumors.

This invention discloses a near-infrared anthocyanin derivative based on boron cluster modification. The anthocyanin unit in the molecular structure of this derivative serves as a near-infrared fluorescence imaging and photothermal conversion unit, possessing not only near-infrared fluorescence imaging capabilities but also the ability to target tumor cells via an organic anion transport peptide-mediated pathway, enhancing selective accumulation in cancerous tissue. The nested carborane structure in the anthocyanin derivative molecular structure utilizes its strong electron-donating properties to induce photo-induced electron transfer with the anthocyanin unit, significantly improving photothermal conversion efficiency while reducing fluorescence quantum yield. The resulting molecule possesses tumor targeting, near-infrared imaging capabilities, and highly efficient photothermal and boron neutron capture therapy functions, achieving synergistic diagnostic and combined therapeutic effects of boron neutron capture therapy (BNCT) and photothermal therapy (PTT) in a single system.

This invention discloses an engineered attenuated Salmonella VNP-SNase, its preparation method, and its applications, including methods and compositions for treating various solid tumors or metastatic tumors. Specifically, engineered attenuated Salmonella capable of expressing and secreting SNase is recruited to the tumor microenvironment through tumor targeting, specifically degrading intratumoral neutrophil extracellular traps (NETs), weakening the killing effect of NETs on Salmonella, increasing its intratumoral colonization, and simultaneously improving the tumor-promoting and immunosuppressive effects caused by NETs, ​​while effectively preventing bacteria from off-target into normal organs. By releasing SNase to activate / regulate the immune system and directly / indirectly inhibit tumors, it can act as an effective immune effector.

The application discloses a preparation method and application of a chemotherapy drug and small interfering RNA tumor-targeting co-delivery nano-therapeutic system, and relates to construction and preparation of a tumor-targeting nano-therapeutic system co-loading a chemotherapy drug, camptothecin, and small interfering RNA (siRac1) targeting Rac1. The application uses N,N-dimethylethylenediamine modified mesoporous polydopamine, loads camptothecin and siRac1, and is then modified by hyaluronic acid to obtain a co-delivery nano-therapeutic system with tumor active targeting. Compared with traditional chemotherapy drugs, camptothecin, the application can realize tumor active targeting drug delivery, and can inhibit tumor chemotherapy resistance mediated by Rac1 by silencing the expression of Rac1 through siRac1, so that the sensitivity of drug-resistant tumor cells to the chemotherapy drug, camptothecin, is restored, tumor drug resistance is reversed, the treatment effect of drug-resistant triple-negative drug-resistant breast cancer is significantly improved, and the application has a good clinical application prospect.

Compositions and methods are provided that enhance CAR T-cell therapy by providing an oncolytic virus engineered to direct expression and secretion of a multivalent adapter protein. The multivalent adapter protein targets both a broadly tumor-associated cell surface antigen and an antigen binding domain of a CAR T-cell.

The present invention relates to a binding protein and use thereof, the binding protein comprising a first binding domain, a second binding domain, and a third binding domain, wherein: the first binding domain is a domain that specifically binds to a tumor-associated antigen (TAA); the second binding domain is both an auxiliary domain that specifically binds to the TAA and a domain that repolarizes the tumor microenvironment (TME) from tolerogenic to pro-inflammatory and, at the same time, specifically binds to an immune checkpoint protein, for in situ T cell priming; and the third binding domain is an effector molecule for inducing T cell response activation and in situ T cell priming in the TME.

The application provides a nano regulator and a preparation method and application thereof. Specifically, water regulation drugs and chemotherapy drugs are co-delivered through metal organic framework nanoparticles or metal polyphenol nanoparticles, the tumor-targeted enrichment and microenvironment-responsive release characteristics of the nano regulator are utilized to release the chemotherapy drugs at the tumor site after cryoablation. The nano regulator can be used for cryoablation sensitization and chemotherapy synergistic treatment, thereby effectively improving the tumor inhibition effect.

The present application relates to the technical field of tumor fluorescence contrast agent, and specifically provides a kind of indocyanine green and multi-arm polyethylene glycol conjugate or its pharmaceutically acceptable salt and preparation method and purposes thereof, the conjugate has the structural formula shown in formula (I), the binding capacity of the conjugate with serum protein is significantly reduced, and the tumor targeting is significantly improved, accumulates and lingers in tumor tissue, to realize targeted treatment or high-resolution imaging, to realize more accurate tumor localization and diagnosis, with very high application value, and open up new method for tumor imaging and treatment development.

The application discloses a sonodynamic nanocatalyst and a preparation method and application thereof, the preparation method constructs a copper-centered organometallic molecule, which adopts an acceptor-donor-acceptor (A-D-A) structure design and can generate active oxygen under ultrasonic stimulation after being prepared into nanoparticles. In order to enhance tumor targeting and immune regulation functions, the sonodynamic nanocatalyst is wrapped with M1 macrophage membranes overexpressing PD-1, and is jointly loaded into a 3D printed bioadhesive GelMA-based hydrogel together with lipid nanoparticles loaded with a targeted CD300ld small interfering RNA, so that precise implantation of the cervical canal is realized. After ultrasonic activation, the system realizes tumor-killing ROS generation and selective silencing of PMN-MDSC-derived immunosuppression.

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.

The present application belongs to the technical field of biological macromolecule pharmaceutical chemistry and tumor targeting delivery system, and particularly relates to a polypeptide conjugate based on linaclotide and a preparation method and application thereof. The present application finds through experiments that linaclotide or its derivative has potential in colorectal cancer (CRC) targeting and deep penetration after proper modification, and therefore proposes a new use of the clinical drug linaclotide or its derivative in a tumor targeting drug delivery system, and constructs a polypeptide conjugate based on linaclotide or its derivative and a tumor targeting drug delivery system based thereon. In-vivo and in-vitro experiments prove that the polypeptide conjugate and the tumor targeting drug delivery system of the present application have precise targeting and deep penetration capabilities in colorectal cancer and metastatic tumors, can effectively enhance the accumulation of an antitumor drug at a tumor site, thereby enhancing the efficacy of the antitumor drug, and have a wide application prospect in the drug delivery system of colorectal cancer.

This invention teaches a tumor-targeting thiocolchicine nanoemulsion wherein the nanodroplets comprising the nanoemulsion are coated with an antinuclear antibody (ANA-nanoemulsion). The nanodroplets are less than 200 nm and will enter the tumor via the Enhanced Permeation and Retention Effect (EPR). Once inside the tumor the antinuclear antibody coating the nanodroplets will bind to extracellular nuclear material released from dead cells and anchor the nanodroplets within the tumor where the drug is released for maximum effect. As all solid tumors have areas of necrosis this means that the ANA-nanoemulsion can target and treat all solid tumors regardless of the tumor type. The ANA-nanoemulsion is formulated to have a phase transition temperature above 8 C. When cooled to below 8 C the ANA-nanoemulsion converts into a suspension of solid lipid nanospheres (ANA-nanospheres) suitable for storage at 4 C or below.

The application discloses a kind of bionic composite nanomedicine and its preparation method and application, which is composed of platelet membrane, chemotherapeutic drug DX8951f And topoisomerase II siRNA;The chemotherapeutic drug DX8951f With topoisomerase II siRNA self-assemble to form composite nanoparticles by electrostatic interaction, and the platelet membrane is coated on the surface of the composite nanoparticles.The application successfully constructs a kind of platelet membrane coated DX8951f With topoisomerase II siRNA The carrier-free bionic nanomedicine, overcomes DX8951f Clinical drug resistance problem by chemotherapy-gene synergistic effect, realizes the stable bionic modification of carrier-free nanoparticle by mechanical extrusion coating process, significantly improves drug in-vivo stability, tumor targeting and biological safety.

The application discloses a targeted cytokine composition for immunotherapy and a preparation method thereof. The fusion protein comprises, from N-terminal to C-terminal, an anti-PD-L1 single-domain antibody, a hinge region, a double-mutated human IL-15, a hinge region, an anti-NKG2D single-domain antibody and a double-mutated human IgG1 Fc fragment. In vitro experiments show that the fusion protein can simultaneously bind to double targets, significantly promotes NKG2D-positive CD8-positive T cell proliferation and has weak effect on regulatory T cells, and presents synergistic effect in a tumor-immune cell co-culture system. In vivo pharmacodynamic research shows that in a humanized mouse model, the fusion protein significantly inhibits the growth of colon cancer, the number of CD8-positive T cell and NK cell infiltrations in the tumor is obviously increased, and the effect is better than that of non-targeting and single-targeting controls. The fusion protein provided by the application has long-acting circulation, tumor targeting enrichment and immune cell subpopulation precise regulation functions, and can be used for preparing an antitumor drug.

This invention belongs to the field of biomedical technology and discloses a paclitaxel reduction-responsive prodrug micelle with high encapsulation efficiency and its preparation method. The paclitaxel-loaded reduction-responsive prodrug micelles prepared in this invention use biocompatible polyethylene glycol (mPEG) and the drug indomethacin (IND) as the hydrophilic and hydrophobic ends of the micelles, respectively, exhibiting synergistic antitumor effects. Simultaneously, it can reverse multidrug resistance to paclitaxel, increase the sensitivity of drug-resistant cells to paclitaxel, and introduce disulfide bonds between the hydrophilic and hydrophobic ends as a linker arm for reduction-sensitive response, responding to the high concentration of GSH in tumor cells to achieve targeted and precise drug release within tumor cells. This prodrug micelle achieves the goals of solubilizing poorly soluble drugs, tumor targeting, and precise drug release at tumor sites, thus enhancing drug efficacy.

This invention discloses the application of a glutamine-depleting engineered bacterium and its pharmaceutical composition. The engineered bacteria use attenuated bacteria with tumor-targeting capabilities as vector strains. The genome or plasmid of the vector strain integrates a therapeutic gene encoding glutaminase. This method achieves deep and continuous depletion of glutamine in the tumor, avoiding drug resistance caused by tumor metabolic compensation. The inhibition rate against c-Myc-overexpressing soft tissue sarcomas is significantly higher than that of small molecule inhibitors. Enzyme production is only carried out locally in the tumor, with no effect on normal tissues and no systemic toxicity. The engineered bacteria can penetrate the dense tumor matrix and colonize the tumor, solving the problem of poor tissue penetration of small molecule inhibitors. The engineered bacteria continuously multiply and produce enzymes in the tumor, achieving continuous release of glutaminase. The half-life is significantly longer than that of recombinant enzymes, eliminating the need for frequent dosing. The glutaminase optimized by protein engineering has significantly reduced immunogenicity.

The present application relates to the technical field of drug evaluation, and discloses a kind of blood tumor targeted drug curative effect dynamic evaluation method and system.The method comprises: by obtaining the feedback parameter containing action index and physiological index after targeted drug administration, and the difference calculation of feedback parameter and the benchmark feedback parameter under the condition of not being administered to output deviation parameter, and then generate drug efficacy fluctuation signal or risk early warning signal;And generate curative effect evaluation report based on drug efficacy fluctuation signal or risk early warning signal.The present application realizes the dynamic quantitative evaluation of curative effect by establishing the benchmark control of patient itself, objectively reflects the net effect of drug on patient, provides reliable individualized data basis for curative effect evaluation, improves the objectivity and accuracy of evaluation;And by filtering out random noise and transient fluctuation in data, ensure that the identified change starting point has high confidence, improve the accuracy and reliability of key event capture in dynamic evaluation process.

The invention relates to a modified aptamer paclitaxel conjugate as well as a preparation method and application thereof. The modified aptamer paclitaxel conjugate comprises paclitaxel, a succinic acid connector and an AS1411 aptamer modified by a G4 ligand. According to the modified nucleic acid aptamer paclitaxel conjugate provided by the invention, the nucleic acid aptamer and paclitaxel are coupled through a connecting bond, and then the nucleic acid aptamer structure is modified by utilizing a G-quadruplex stabilizer through a chemical method, so that the target conjugate is obtained; and finally, the compound specifically targets tumor cell surface protein and has anti-cancer activity, so that the compound is used for treating cancers.