24 results about "Tumor selectivity" patented technology

Antibodies are provided which comprise at least one Fab portion that binds CD47 and at least one Fab portion that binds the tumor associated antigen (TAA) CD20; wherein the Fab portion that binds CD47 exhibits low affinity for CD47; and, wherein the Fab portion that binds CD20 exhibits high affinity for CD20; and, wherein the antibody selectively binds CD47 and blocks CD47 interaction with SIRPα in tumor cells while exhibiting no substantial binding to CD47 in normal cells.

The invention relates to the technical field of pathological diagnosis, in particular to a tumor grading detection system based on holoproteome cysteine reactivity analysis, which comprises an in-situ labeling module, an in-situ detection module and an in-situ detection module, the histological separation module is used for carrying out molecular weight layering separation on the labeled tumor protein and counting the fluorescence signal intensity of each layer; the processing and analysis module is used for constructing a proteome-level cysteine reactivity map with position resolution capability; the tumor grading module is used for carrying out normalization processing on the average fluorescence intensity of each layer and the highest signal layer to obtain normalized intensity T, drawing a component specificity risk curve by taking the number of layers as a horizontal coordinate, and recording the area under the curve as the normalized intensity T as TSI; the TSI is in positive correlation with the tumor malignancy degree and serves as the basis of tumor grading. The method can accurately diagnose a tumor positive area, and the specificity and the sensitivity are both 100%.

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.

The application belongs to the technical field of biomedicine, and relates to a mitochondrion-targeted nano device and a preparation method and application thereof, the nano device comprising a cascade-activated photodynamic molecular beacon and a mitochondrion-targeted delivery carrier, the cascade-activated photodynamic molecular beacon comprising an APE1 cleavage site and a microRNA recognition region. The cascade-activated photodynamic molecular beacon and the mitochondrion-targeted delivery carrier are self-assembled into a complex through electrostatic adsorption, and cascade activation and signal amplification are realized through the dual response of miR-146a / APE1 which is highly expressed in mitochondria of tumor cells. The application triggers precise and controllable cell pyroptosis through tumor-specific signals, reverses the immune-inhibitory microenvironment, converts the 'cold tumor' into a 'hot tumor', significantly improves the effect of cancer immunotherapy, has good biocompatibility and tumor selectivity, and provides a new strategy and tool for precise treatment of cancer.

The application provides a resiquimod prodrug and a preparation method and application thereof. The resiquimot prodrug comprises a carrier and a riboflavin derivative loaded on the carrier. The carrier is obtained by bonding R848-TK and mPEG-PHEA. b The application uses R848 NPs as a carrier to physically load a liposoluble riboflavin derivative, and is used for constructing an ultrasound-activated resiquimot prodrug. The riboflavin derivative is a liposoluble substance, can be activated under ultrasound conditions, and then generates 1 O2, is used for cutting the TK bond, thereby releasing the active drug R848. The application can effectively enhance the tumor selectivity of the drug and realize a time-space controllable precise treatment by preparing a more specific ultrasound-activated resiquimot prodrug.

A combination therapeutic strategy employs multiple oncolytic viruses (OVs), grouped and administered based on their virological properties, tumor selectivity, and distinct antigen profiles, to treat malignant tumors. Representative groupings may include members of flaviviruses, each contributing distinct immune modulation and the same modes of tumor cell killing. A predefined treatment schedule involves sequential or concurrent administration of antigenically diverse OVs in multiple cycles, reducing cross-neutralization and sustaining cytolytic pressure on tumors. A pre-characterized OV panel, comprising members from a virus family, RNA and DNA viruses, both wild-type and genetically engineered, serves as a flexible resource for customizing treatment regimens by tumor type, immune landscape, and therapeutic goals. This platform establishes a rational framework for combination OV therapy with improved durability, safety, and clinical effectiveness.

The invention discloses a compound or pharmaceutically acceptable salt thereof as well as a preparation method and application thereof. The invention further discloses 22 compounds of the type and a chemical synthesis method thereof, the synthesis route is simple, operation and implementation are easy, and needed reagents are easy to purchase. The novel DIQ01 and the derivative thereof found in the invention can be specifically combined with a target protein KHSRP and inhibit the function of the target protein KHSRP, and the structure type is novel; compared with a plurality of clinical drugs, the compound shows better tumor anti-proliferation activity, and has good tumor selectivity and a wide treatment window. The compound and the pharmaceutical composition thereof can be used for preparing medicines for treating various tumors, and are preferably used for preventing or treating solid tumors such as colorectal cancer, breast cancer, lung cancer and the like and hematological malignant tumors.

The present invention relates to a chimeric poxvirus with improved anticancer activity (higher cancer cell killing capacities and better tumor selectivity), as well as variant version thereof with one or more altered viral genes, recombinant versions thereof comprise one or more nucleic acid(s) of interest and recombinant variant versions thereof, all of which may be included in a composition and used for the treatment of a disease, in particular proliferative disease, notably cancers.

This invention discloses a sensitizer for PD-1 antibody drugs and its application, as well as an antitumor drug composition and its application. The sensitizer comprises dihydroartemisinin and niraparib, and the antitumor drug composition comprises dihydroartemisinin, niraparib, and a PD-1 antibody. This invention is the first to experimentally discover that dihydroartemisinin possesses a dual mechanism of action: "non-HRD-dependent PD-L1 upregulation" and "tumor-selective ferroptosis induction." This mechanism complements and synergizes with niraparib's "HRD-dependent PD-L1 upregulation + synthetic lethality" mechanism and the PD-1 antibody's "immune activation" mechanism. The antitumor drug composition formed by combining these three components can effectively reshape the tumor immune microenvironment, exerting a potent antitumor effect by upregulating PD-L1 expression in tumor cells, increasing the number of cytotoxic T cells, and inhibiting the proportion of regulatory T cells.

The invention belongs to the technical field of biomedicine, and particularly relates to an enhanced specific promoter and application thereof. In order to solve the problems that the safety of ICP6 wild herpes virus is poor, the replication ability of ICP6 defective virus is poor, and the oncolytic effect needs to be improved, the invention provides a core starting element, the nucleotide sequence of which is as shown in SEQ ID NO.5; or a nucleic acid molecule which has one or more base insertion, deletion and / or substitution mutation in a nucleotide sequence shown in SEQ ID NO.5 and still has a promoter function. The core promoter element or promoter can specifically express the ICP6 gene in tumor cells infected with the herpes simplex virus, so that the replication capacity of the recombinant oncolytic virus is improved, the oncolytic activity and tumor selectivity of the recombinant oncolytic virus are improved, and the core promoter element or promoter also shows relatively good safety in a mouse model; the method is suitable for developing oncolytic viruses or virus vectors.

The application discloses a nano-focal anaphylaxis drug targeting CD47 protein and preparation and application thereof, and belongs to the technical field of drugs. The nano-focal anaphylaxis drug is a micellar nanoparticle formed by self-assembly of an amphiphilic carrier material and a focal anaphylaxis prodrug, the amphiphilic carrier material is composed of an amphiphilic polymer with a hydrophilic end modified with a CD47 targeting peptide and an amphiphilic polymer without modification, and the focal anaphylaxis prodrug is a prodrug formed by reduction response chemical bond connection of lonidamide or 3-bromopyruvic acid. The nano-focal anaphylaxis drug provided by the application can realize precise tumor treatment, the CD47 targeting peptide realizes efficient targeted delivery and accumulation of the drug in the tumor, the release of the focal anaphylaxis prodrug is triggered by higher reduction medium level in tumor tissues, and tumor cells are induced to undergo focal anaphylaxis. In normal tissues, the nano drug cannot induce normal cell focal anaphylaxis, and therefore the tumor selectivity of the nano drug is significantly enhanced.

The application discloses a fluorinated monosaccharide derivative and a synthesis method and application thereof. The fluorinated monosaccharide derivative is composed of three parts, the first part is a 1-substituted monosaccharide group, the second part is a fluorine signal source perfluoro-t-butyl ether group, and the third part is a triazole ring connecting the two. The fluorinated monosaccharide derivative of the application retains the 2-hydroxyl and 6-hydroxyl of the monosaccharide, thereby not affecting the recognition of the monosaccharide in the body, and having good water solubility and biocompatibility. The derivative contains nine magnetically equivalent fluorine-19, can produce a single and strong fluorine signal, and avoids problems such as fluorine signal splitting or low fluorine atom utilization. The fluorine signal strength has a good linear relationship with the concentration of the compound, which provides a basis for in vivo quantification 19 F MRI. 19 F MRI imaging of HepG2 cells has the potential to be used as a tumor selective 19 F MRI contrast agent.

The invention belongs to the field of biological medicine, and particularly relates to construction of a tumor targeted delivery system for in-situ synthesis of an apoptosis inducer and application of the tumor targeted delivery system in apoptosis-copper death synergistic treatment. The synergistic mitochondrial injury is realized through combined treatment of apoptosis-copper death mediated by small molecule CTT for inducing tumor cell apoptosis. CTT is synthesized in situ in a tumor through a biological orthogonalization method. In order to improve the tumor selective synthesis efficiency, reduce the off-target effect and overcome the problems of rapid removal and metabolism of the drug, the corresponding precursor drug is delivered by adopting a ZIF-8-based nano material. Under the acidic condition of a tumor microenvironment, PVP (at) CuP (at) ZIF is decomposed and releases Cu (I) ions and a prodrug, and in-situ synthesis of CTT is realized by means of a Cu (I) catalytic azide-alkyne cycloaddition reaction. Based on in-situ synthesis with high tumor selectivity, the invention provides a novel method for overcoming tumor drug resistance through apoptosis-copper death combined pathway mediated synergistic mitochondrial damage.

The invention provides, e.g., a recombinant virus comprising (i) a modified TATA box-based promoter, and / or (ii) a modified CAAT box-based promoter operably linked to a gene, wherein the modified TATA box-based promoter and / or modified CAAT box-based promoter lacks a functional TATA box and / or CAAT box and permit selective expression of the gene in a hyperproliferative cell. The recombinant viruses can be used to treat cell proliferative diseases and disorders, including certain forms of cancer.

The invention relates to an X-ray controllable activation nanoparticle as well as a preparation method and application thereof, and relates to the technical field of biological medicines. The technical problems that in the existing radiotherapy sensitization process, NO whole body delivery lacks tumor selectivity, toxicity is large, and radiotherapy specific release cannot be achieved are solved. The nanoparticle comprises a polymer carrier, a nitric oxide donor entrapped in the polymer carrier and a targeting molecule modified on the surface of the nanoparticle, the polymer PEG-PCL carrier is an amphiphilic block copolymer; the nitric oxide donor is BNN6; the targeting molecule is a GRP78 targeting peptide. The nanoparticle is a delivery system capable of realizing GRP78 targeting and X-ray activated NO release at the same time, can actively target radiotherapy to resist tumors, and can trigger to release NO only under X-ray irradiation so as to realize safe and efficient radiotherapy sensitization.

The invention discloses a double-response type self-assembly multivalent DNA (deoxyribonucleic acid) nanogel as well as a preparation method and application thereof. The tumor selectivity is realized by triggering depolymerization and FEN1 cutting through the dual response markers, and the multivalent structure can target single / multiple mRNA targets (such as KRAS, PDL1 and FUT8) at the same time. The DNA nanogel disclosed by the invention has a self-delivery capability, does not need an exogenous carrier, has low toxicity to normal cells, and has an application prospect in tumor gene therapy.

The invention discloses a preparation method and application of a selenium-containing photosensitizer based on a quinoline skeleton, the structure of the organic photosensitizer is shown in the specification, the invention develops a novel photosensitizer PDSe series based on selenium atoms, and the photosensitizer can be used for preparing the selenium-containing photosensitizer through unique D-pi-A structural design and the heavy atom effect of the selenium atoms. And an efficient photodynamic therapy effect is achieved. Active oxygen generated by the photosensitizer after illumination activation can directly kill tumor cells and also can significantly enhance the anti-tumor effect through a concentration-dependent dual action mechanism (low-concentration apoptosis induction and high-concentration pyroptosis induction), and the dynamic regulation mechanism not only improves the treatment effect, but also reduces the drug resistance risk of the tumor cells. Particularly, by introducing the PDSE-8 derivative designed by a targeting ligand, mitochondria can be accurately targeted, an overexpressed receptor on the surface of a tumor cell can be recognized, and the tumor selectivity and the drug delivery efficiency are remarkably improved.

The present disclosure provides a method for treating cutaneous neurofibromas (cNFs) in patients with neurofibromatosis type 1 (NF1) using talimogene laherparepvec (T-VEC), an oncolytic herpes simplex virus 1 (oHSV1) vector, as an illustrative example. The method includes administering to a subject an effective amount of T-VEC, typically by intratumoral injection. T-VEC is genetically modified to enhance tumor selectivity and stimulate anti-tumor immune responses. The treatment involves an initial dose followed by subsequent doses at specified intervals. The method may include repeated administrations and combination with additional therapies for cNF or NF1. This approach offers a potential non-invasive alternative to current treatments for cNFs in NF1 patients.

The invention discloses a sensitizer of a PD-1 antibody drug, an application of the sensitizer, an anti-tumor drug composition and an application of the anti-tumor drug composition. The sensitizer is prepared from dihydroartemisinin and niraparil, and the anti-tumor medicine composition is prepared from dihydroartemisinin, niraparil and a PD-1 antibody. It is found through experiments for the first time that dihydroartemisinin has a double-acting mechanism of'non-HRD dependent PD-L1 up-regulation 'and'tumor selective ferroptosis induction', and functional complementation and effect synergy are formed by dihydroartemisinin, an'HRD dependent PD-L1 up-regulation + synthetic lethal 'mechanism of nirapalide and an'immune activation' mechanism of a PD-1 antibody. The antineoplastic pharmaceutical composition formed by combined use of the three can effectively remodel a tumor immune microenvironment, and synergistically exerts a powerful antineoplastic effect by up-regulating expression of tumor cells PD-L1, increasing the number of killer T cells and inhibiting the proportion of regulatory T cells.

The application discloses 2-amino-8-hydroxyquinoline nickel complexes for resisting drug-resistant ovarian cancer and a preparation method thereof. The application takes 2-amino-8-hydroxyquinoline as a first ligand, and takes 4,7-dichloro-1,10-phenanthroline, 5 5'-dimethyl-2,2'-dipyridyl, 5-chloro-phenanthroline, 4,4'-dimethoxy-2,2'-dipyridyl, 1,10-phenanthroline-5-amino, 1,10-ortho-phenanthroline, 2,9-dimethyl-ortho-phenanthroline (L7) and 4,7-diphenyl-1,10-phenanthroline as auxiliary ligands, synthesizes eight kinds of 2-amino-8-hydroxyquinoline nickel complexes (Ni-1-Ni-8) for treating drug-resistant strain cells of ovarian cancer. Experimental results show that Ni-1-Ni-8 has good inhibiting effect on ovarian cancer drug-resistant strain cells SK-OV-3 / DDP, and the toxicity of the normal HL-7702 cells is much smaller than that of tumor cells, which indicates that the complexes have good tumor selectivity on tumor cells, exhibit superior anti-tumor activity, have potential medicinal value, and are expected to be used for preparing various anti-tumor drugs.

This invention relates to Furin / hydroxyl radical dual-responsive size-changing nanoparticles, their preparation, and applications. The Furin / hydroxyl radical dual-responsive size-changing nanoparticles use an AIE photosensitizer as the core and DSPE-PEG as the substrate. 2K MAL nanoparticles serve as carriers, with functional peptides coupled to their surfaces via Michael addition reactions. The core functional building block is a self-designed and custom-synthesized R1 peptide, which possesses a triple function: high specificity recognition by Furin protease, OH-responsive tyrosine oxidation cross-linking, and coupling with DSPE-PEG nanoparticles. Its simple sequence significantly enhances tumor selectivity. The peptide is covalently modified with natural peptides using a nanoprecipitation method, avoiding complex chemical modifications and exogenous orthogonal biological groups, thus mitigating the toxicity and synthesis costs of traditional systems. Under the dual conditions of Furin protease overexpression and the presence of OH, size transformation is triggered, enabling deep tumor penetration with small sizes and long-term intratumoral retention through in-situ large-size assembly, demonstrating clinical translational potential.

This invention discloses the application of serine in the preparation of drugs for treating pancreatic ductal adenocarcinoma (PDAC), belonging to the field of biopharmaceutical technology. This invention provides the application of serine in the preparation of drugs for treating PDAC. This invention discovers that serine overload can selectively inhibit PDAC cell proliferation. Mechanistic studies show that serine overload induces a "glutamine functional deprivation" state, synergistically regulating tumor cell metabolic reprogramming, redox homeostasis, and anti-tumor immune responses, constructing a tumor-selective metabolic intervention mode. Results from specific embodiments of this invention show that serine overload can achieve therapeutic effects on pancreatic ductal adenocarcinoma both in vivo and in vitro. Therefore, this invention provides a new theoretical basis and potential combination therapy ideas for anti-tumor intervention strategies targeting amino acid metabolism and targeted therapy for PDAC.

The invention relates to an IRE electrical sensitization nanometer material capable of regulating and controlling a tissue dielectric constant, a manganese carbonate nanometer material is manganese carbonate nanometer particles, the manganese carbonate nanometer particles are of a rhombohedral structure, and the average particle size is about 100-200 nm. According to the invention, the IRE ablation efficiency and tumor selectivity are obviously improved, and the residue and recurrence risk is reduced; economically, expensive equipment and complex processes are not needed, and the cost is controllable; in society, prognosis of patients is improved, life quality is improved, and safe and efficient treatment of solid tumors such as liver cancer is promoted.