73 results about "Folate receptor" patented technology

The invention provides a folate receptor targeting small molecule compound, a preparation method, a composition and application. Specifically provided is a compound represented by formula I or a pharmaceutically acceptable salt thereof. The compound or the pharmaceutically acceptable salt thereof provided by the invention can be used as a small-molecule targeting fluorescence contrast agent for assisting surgical treatment, has the advantages of novel structure, good solubility, small steric hindrance and strong targeting property, can obviously improve the view field of tumor surgery, and is beneficial to efficiently and accurately implementing excision of pathological tissues such as tumor tissues, boundary tissues and the like. # imgabs0 #

The present invention provides, inter alia, antibody-drug conjugates (ADCs) that specifically bind to folate receptor-I (FOLR1). Pharmaceutical compositions and methods for treating cancer are also disclosed.

The invention provides application of a near-infrared fluorescent probe of a targeted folate receptor in preparation of a near-infrared first region and near-infrared second region diagnostic drug, and relates to the technical field of organic fluorescent molecules. The folate receptor-targeted near-infrared fluorescent probe has a structural formula as shown in a formula I which is described in the specification. The near-infrared fluorescent probe provided by the invention has good tumor targeting capability and water solubility, also has near-infrared two-region developing capability, and has huge development potential and application prospect in fluorescence-guided intraoperative navigation. # imgabs0 #

The present invention relates to an antibody-drug conjugate, wherein the antibody specifically binds to the folate receptor a and the drug is preferably selected from among cytotoxic drugs. Such antibody-drug conjugates are particularly useful in the treatment of proliferative diseases, including cancers such as ovarian cancer, breast cancer and non-small cell lung cancer.

The invention belongs to the field of biological medicine, and relates to a human serum albumin covalent binding type targeted folate receptor micromolecule drug conjugate prodrug and application thereof. The prodrug disclosed by the invention has a structure as shown in a formula I, six-carbon maleimide is used as a site combined with endogenous albumin, and albumin is used as a carrier to deliver the drug. The prodrug can increase accumulation of the drug in tumors under the EPR effect. A dipeptide chain composed of valine and alanine is used as a cleavage site of cathepsin B, an adapter composed of p-aminobenzyl ether and N-methylamino-4-nitrophenol releases drugs in an acidic environment, an azidohexanoic acid structure is added to a side chain of p-aminobenzyl ether, so that the site of a targeting ligand can be increased, and SN38 is used as a small molecule cytotoxic load. The micromolecular prodrug has dual functions of active targeting and passive targeting, and can effectively improve the concentration in solid tumors, reduce toxic and side effects and improve the anti-tumor effect under the mediation of related receptors.

The invention discloses a lipidosome drug delivery system for targeted therapy of brain glioma and application thereof. The lipidosome drug delivery system is a lipidosome mixture prepared from a basic component, a functional component and an external water-phase buffer solution. After intravenous injection, the liposome is efficiently combined with complement protein C3 and immune globulin M in plasma to synergistically activate a complement system, actively attracts and activates neutrophils to uptake, and crosses a blood brain barrier in a mode of'building a defecation vehicle 'by utilizing the inflammatory taxis of the neutrophils. Neutrophile granulocytes are stimulated by inflammatory factors in a microenvironment after reaching a tumor brain area to form extracellular trap release lipidosome. The lipidosome realizes specific targeting through folate receptors over-expressed on the surfaces of glioma cells. The liposome shows excellent cross-blood-brain-barrier drug delivery efficiency and brain glioma curative effect in vivo, can be effectively combined with surgery, radiotherapy and the like, and provides a solution for the main problems of radiotherapy resistance, chemotherapy drug resistance and the like in clinic.

A conjugate comprising a ligand that targets a folate receptor linked to an acrolein scavenger drug; a composition comprising same; a method of using the conjugate or the composition to scavenge acrolein, alone or in further combination with other reactive aldehyde species, in a subject with neurotrauma; and a method of delivering an acrolein scavenger or an imaging agent to the central nervous system (CNS) of a patient with inflammation in the CNS.

The invention discloses a near-infrared fluorescence imaging agent of a targeted folate receptor, an imaging system and application of the imaging agent and the imaging system, and belongs to the technical field of biomedical treatment. The technical problem to be solved is to provide the folate receptor-targeted near-infrared fluorescence imaging system, an imaging agent in the system can specifically target the folate receptor FR-alpha, and the folate receptor-targeted near-infrared fluorescence imaging system is used in application scenes of lung cancer and ovarian cancer and can show higher TNR, display tumor boundaries in real time and reduce the positive edge cutting rate. According to the technical scheme, the near-infrared fluorescence imaging agent of the targeted folic acid receptor is characterized by comprising a compound of the targeted folic acid receptor, a solvent and pharmaceutically acceptable auxiliary materials, the structure of the compound of the targeted folic acid receptor is F-L-D, F is the structure of the targeted folic acid receptor, D is a near-infrared dye, L is a connexon, and L is an electron donor. The structural formula is shown in the specification or pharmaceutically acceptable salts thereof.

The present disclosure provides a class of compounds including a ligand moiety that specifically binds to a cell surface receptor, such as a folate receptor. The cell surface folate binding compound can trigger the receptor to internalize into the cell a bound compound. The ligand moieties of this disclosure can be linked to a variety of moieties of interest without impacting the specific binding to, and function of, the cell surface receptor, e.g., folate receptor. Also provided are compounds that are conjugates of the ligand moieties linked to a biomolecule, such as an antibody, which conjugates can harness cellular pathways to remove specific proteins of interest from the cell surface or from the extracellular milieu. Also provided herein are methods of using the conjugates to target a polypeptide of interest for sequestration and / or lysosomal degradation.

Provided herein are bifunctional lysosomal targeting degraders that comprise folate or a folate analog configured to bind to folate receptor as a shuttle molecule for lysosome degradation, and a protein binder configured to bind a membrane or extracellular protein of interest. The bifunctional degraders find use, e.g., for selectively targeted degradation of membrane and extracellular proteins via the endosomal / lysosomal pathway. Also provided herein are compositions comprising the bifunctional degraders, as well as methods of using the bifunctional degraders.

The invention discloses a complement amplification folic acid optical fiber sensing system and a folic acid concentration detection method thereof. The sensing system comprises an excitation light source, an optical fiber sensing probe, a micro-fluidic plate, a nanogold rod amplification solution and a spectrograph, the excitation light source, the optical fiber sensing probe and the spectrograph are sequentially communicated, the optical fiber sensing probe is introduced into the micro-fluidic plate, the nanogold rod amplification solution is introduced into the micro-fluidic plate, and the nanogold rod amplification solution is introduced into the spectrograph. The optical fiber sensing probe is a folic acid receptor protein modified gold-plated film optical fiber, and the nanogold rod amplification solution is a folic acid modified nanogold rod solution. Under the participation of the gold nanoparticles, the optical fiber sensing probe realizes enhanced plasma resonance wavelength shift, so that the sensitivity of folic acid molecule detection is remarkably improved, folic acid in a solution can be quickly and directly measured, and the application range is wide.

Disclosed in the present invention are a fluorescent molecule targeting a folate receptor, a preparation method therefor and the use thereof. The present invention provides a compound represented by formula (I), a pharmaceutically acceptable salt thereof, or a tautomer thereof. The compound of the present invention can be used as a fluorescent contrast agent in near-infrared surgical navigation.

The invention provides a dual-targeting nano-material photosensitizer for cervical cancer as well as a preparation method and application of the dual-targeting nano-material photosensitizer. The folic acid modified poly-beta-cyclodextrin (poly-beta-CD) is used as a nano-carrier and is used for loading a photosensitizer PAP (PAP is pyropheophorbide a covalently connected PAAKRVKLD) coupled with a nuclear localization signal (NLSs). The finally prepared FA-CD-coated PAP nano material can specifically recognize cervical cancer cells of overexpressed folate receptors (FR), so that accumulation in tumor cells is remarkably enhanced. In addition, the encapsulated PAP can achieve accurate cell nucleus localization. Under an illumination condition, reactive oxygen species (ROS) generated by PAP accumulated in nuclei can instantly oxidize and damage a DNA chain or DNA repair enzyme, so that cell death is directly induced, and the anti-tumor effect of targeted photodynamic is greatly enhanced. The novel dual-targeting nano drug-loading system prepared by the invention solves the problems of poor targeting and biological solubility and limited treatment effect of a traditional photosensitizer, and provides an innovative intelligent targeting delivery strategy for in-situ cell nucleus photodynamic therapy.

The invention relates to a folic acid conjugate as well as a preparation method and application thereof. Specifically, the invention discloses a novel folic acid conjugate and a drug combination strategy thereof, and also provides a preparation method of the conjugate and an application of the conjugate in tumor treatment. The conjugate provided by the invention has folate receptor expression dependence, can efficiently inhibit ovarian cancer cell proliferation, and shows a good action effect when being combined with a DNA (Deoxyribose Nucleic Acid) damaging agent.

The application provides a folate receptor targeted drug, a metal complex and a preparation method and application thereof, and relates to the technical field of radio labeling. The folate receptor targeted drug has a structure as shown in formula I, and a metal complex is prepared after being labeled by a radionuclide. The folate receptor targeted drug or the metal complex provided by the application can be used for diagnosing and / or treating diseases with overexpression of folate receptors. The folate receptor targeted drug has the advantages of high in-vivo stability, strong specificity, good targeting property and the like.

The present invention relates to the fields of radiopharmaceutical chemistry and clinical nuclear medicine technology, and specifically to a D-proline-modified folate derivative and its use. The radioactive preparation obtained by labeling the D-proline-modified folate derivative with a radionuclide can be prepared by kitting. It has high radiochemical purity and good stability. It exhibits significant uptake at the tumor site in tumor-bearing mice, is significantly inhibited by inhibitors, has a good target / non-target ratio, and exhibits low renal uptake. It can be used as a novel tumor imaging agent targeting folate receptors.

This invention discloses a folic acid receptor-targeting compound and its uses, belonging to the field of pharmaceutical technology. The folic acid receptor-targeting compound is a compound of formula (I), its stereoisomer, its crystalline hydrate, its deuterated derivative, its solvate, its prodrug, or a pharmaceutically acceptable salt thereof: [target]-(L x ) s -R x (I), where [target] is a folic acid receptor-binding ligand; R x The chelating group is Ch or the prosthetic group is PG; s is an integer from 1 to 10; L x It contains at least one L 3 and with AA, L 1 L 2 or L 3 Arbitrary combinations are possible. The folic acid receptor-targeting compounds of this invention have low KD values ​​and strong affinity between the ligands and receptors, and can be used as folic acid receptor-targeted radiotherapy agents for imaging, diagnosis, and treatment of folic acid receptor (FR)-expressing tumors or cells.

The invention discloses a compound and a composition of a targeted folate receptor as well as a preparation method and application of the compound and the composition, and belongs to the technical field of medical biology, the compound of the targeted folate receptor is F-L-D, F is a structure of the targeted folate receptor, D is a near-infrared dye, L is a connexon, and the structural formula is shown in the specification or a pharmaceutically acceptable salt thereof. The compound of the targeted folate receptor is used as a targeted near-infrared fluorescence imaging agent, can be matched with a near-infrared fluorescence imaging system for use, can specifically target the folate receptor FR-alpha, and is used for auxiliary diagnosis of identifying malignant lesions in a tumor patient operation. In application scenarios of lung cancer and ovarian cancer, the compound can show higher TNR and can display tumor boundaries in real time so as to help to identify intraoperative lesions, reduce the positive edge cutting rate and the false positive rate and realize accurate excision.

The application belongs to the field of biological medicine, and provides a tumor microenvironment responsive nano-drug, which comprises a ferrous metal organic framework, polyethylene glycol / leafy on the modified ferrous metal organic framework and PK11195 encapsulated in the metal framework, and a structural formula of the PK11195 is as shown below. The application also provides a preparation method of the tumor microenvironment responsive nano-drug. The application also provides the use of the tumor microenvironment responsive nano-drug in the preparation of a drug for treating hepatocellular carcinoma. The nano-drug can be actively targeted to tumor cells by combining with folate receptors, under the guidance of MRI, and rich ROS is generated by the irradiation of near-infrared light, so as to induce cell ICD, which provides a prospect for promoting systemic antitumor photodynamic therapy and immunotherapy.

Disclosed is an antibody that specifically recognizes and binds to folate receptor α, also referred to as anti-folate receptor a antibody or anti-FRα antibody. Also disclosed is an antibody-drug conjugate of the anti-FRα antibody. Disclosed are uses of the anti-FRα antibody and the antibody-drug conjugate in the treatment of diseases related to FRα expression.

The invention provides a monoclonal antibody of a folic acid and folic acid receptor protein compound and application of the monoclonal antibody. The sequences of heavy chain variable regions CDR1, CDR2 and CDR3 are respectively shown as SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8, and the sequences of light chain variable regions CDR1, CDR2 and CDR3 are respectively shown as SEQ ID NO: 10, SEQ ID NO: 11 and SEQ ID NO: 12. The antibody can be used for double sandwich method detection of folic acid, and has good detection sensitivity and detection linear range.

The invention discloses an anti-cervical cancer nano targeting tablet based on a traditional Chinese medicine compound and a preparation method thereof. The nano targeting tablet is prepared from the following raw materials in parts by weight: centipede, bungarus parvus, syngnathus, scorpio, nidus vespae, leech, ground beeltle, frankincense, myrrh, dandelion, rhizoma cyperi, radix bupleuri, fructus aurantii, cortex phellodendri, angelica sinensis, radix curcumae, poria cocos, bighead atractylodes rhizome, radix paeoniae alba, cortex albiziae, Chinese yam, oldenlandia diffusa and selfheal. According to the invention, active ingredients of the traditional Chinese medicinal materials are retained and enriched to the maximum extent through a modern extraction technology, the curative effect of the original formula is ensured to be retained to the maximum extent, and through a folic acid receptor, CD44 receptor and pH sensitive triple targeting mechanism, the medicine is enriched in cervical cancer tissues, the local medicine concentration is improved, the system toxicity is reduced, and accurate targeting delivery is realized.

The present application relates to the field of medical diagnosis, and provides a combined marker for predicting the curative effect of target immune drug for primary liver cancer and application thereof, wherein the combined marker is folate receptor gamma gene FOLR3, stratified protein gene SFN and coiled-coil domain containing 9 gene CCDC9 derived from peripheral blood leukocyte mRNA.The present application performs combined detection based on multiple peripheral blood leukocyte markers, and compared with a single molecular marker, can reduce errors caused by individual expression difference of a single index to some extent, so that the detection result is more accurate.The curative effect prediction model constructed based on detection of peripheral blood leukocyte mRNA level change can specifically recognize and detect in the early stage of tumor formation, has high sensitivity and high specificity, provides an important means for reasonable use of target immune drug for liver cancer patients sensitive or resistant to target immune drug, and has great significance for effective treatment of liver cancer in China.

The application discloses a kind of lysosome-targeting protein modulators based on upconversion nanomaterial-DNA nanostructure and preparation method thereof.The lysosome-targeting protein modulators are combined by covalent bond from carboxyl functionalized upconversion nanoparticles and amino-modified DNA nanostructure, mainly enter cancer cells through folate receptor, after near infrared light illumination and glutathione response, the target protein combined is transported into lysosome and degraded.The lysosome-targeting protein modulators of the application have the advantages of light affinity, high controllability and storage stability, are easy to be metabolized by organism, and have good application prospect in the field of cell biology and cancer targeted therapy.

Photodynamic therapy (PDT) is a minimally invasive treatment that involves the administration of a light-activatable drug followed by light activation of the lesion to produce reactive oxygen species that kill cancer cells. VISUDYNE®, a liposomal formulation of benzoporphyrin derivative (BPD) photosensitizer, is clinically approved for PDT of ocular diseases and is now being tested for PDT and imaging of pancreatic, brain, and other cancers. While VISUDYNE® improves the pharmacokinetics of BPD, it lacks treatment selectivity. This present disclosure is directed to dBPD, dBPD nanoparticles, and preparation and use thereof that provide cancer treatment selectivity for cancers characterized by overexpression of folate receptor (FR).

The present invention relates to antibody-drug conjugates, wherein the antibody specifically binds to folate receptor a, and wherein the drug is preferably chosen among a cytotoxic drug. Such antibody-drug conjugates are useful in particular in treating proliferative diseases including cancers, such as ovarian, breast and non-small cell lung cancers.

The present invention relates to novel binding proteins specific for folate receptor alpha (FOLR1). The present invention also relates to FOLR1 binding proteins further comprising diagnostically or therapeutically active ingredients. Further aspects of the present invention relate to the use of these FOLR1 binding proteins in medicine, for example in the diagnosis and treatment of FOLR1-related cancers.

The disclosure provides a liposomal antifolate composition comprising a liposome including an interior space, a bioactive antifolate agent disposed within said interior space, a steric stabilizer attached to an exterior of the liposome, and a targeting moiety comprising a protein with specific affinity for at least one folate receptor, said targeting moiety attached to at least one of the steric stabilizer and the exterior of the liposome.

The invention discloses a folate receptor mediated reduction-released dual-targeting curcumin polymer micelle and a preparation method thereof. A tumor target molecule folic acid is modified on a biodegradable hydrophilic polyethylene glycol skeleton, and is coupled with curcumin through a disulfide bond to construct an amphiphilic polymer monomer with a high grafting rate, and the molecular formula of the amphiphilic polymer monomer is FA-PEG2K-SS-CUR; the curcumin micelle is prepared by self-assembly through a dialysis method, so that a traditional encapsulation drug loading mode is simplified, the drug is a part of a carrier, and drug leakage is avoided. The polymer micelle obtained by the method has high drug loading rate, stability and biocompatibility, improves the solubility of curcumin in water, enhances the targeted release of tumor cells, reduces the toxic and side effects, and has a higher antitumor effect than the bulk drug.

The invention relates to the technical field of biological materials, particularly provides folic acid-DOTA dual-functional nanoparticles for early-stage MRI (magnetic resonance imaging) detection of cancers, and also provides a preparation method of the folic acid-DOTA dual-functional nanoparticles and application of the folic acid-DOTA dual-functional nanoparticles in contrast imaging. The folic acid-DOTA dual-functional nano-particle provided by the invention comprises a hollow silicon dioxide nano-particle, the folic acid-PEG-maleimide and the DOTA-Gd are loaded on the surfaces of the hollow silicon dioxide nano particles. According to the invention, folic acid-PEG-maleimide is modified on the surfaces of hollow silicon dioxide nanoparticles, and specific enrichment of the MRI contrast agent in lung cancer tissues is realized by using a folic acid receptor mediated active targeting mechanism; meanwhile, by loading DOTA-Gd on the surface, the effective imaging window time is prolonged, the release risk of free gadolinium ions is reduced, and a safe and efficient nano radiography system is provided for precise diagnosis of lung cancer.