53 results about "Folate receptor" patented technology

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 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.

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.

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 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.

The invention belongs to the field of functional nano-materials, and particularly relates to a silicon-based mesoporous nano-drug delivery system with folic acid modified on the surface and a preparation method and application thereof. The preparation method comprises the steps of mesoporous silicon synthesis, amino modification, folic acid grafting, drug impregnation and the like, and further comprises preferable schemes such as metal doping (Fe, Cu) and the like. The drug delivery system significantly improves the stability and bioavailability of a part of insoluble drugs. Meanwhile, aiming at the microenvironment characteristics that tumor tissues are acidic and rich in folic acid receptors, the drug delivery system realizes dual functions of pH responsiveness and initiative through folic acid modification, so that the damage to normal tissues is effectively reduced, and accurate delivery and controllable release of drugs at tumor parts are realized. According to the technical scheme, a new solution is provided for clinical application of indissolvable drugs, and the pharmaceutical composition can be used for treating various diseases.

The invention discloses a folic acid modified NK cell-derived exosome entrapped oncolytic reovirus compound as well as a preparation method and an application of the folic acid modified NK cell-derived exosome entrapped oncolytic reovirus compound. In the compound, folic acid and an NKexo phospholipid bilayer modify NKexo in a self-assembly insertion manner; in the compound, Reo is loaded into NKexo through an extrusion method. The method comprises the following steps: extracting NKexo, modifying the NKexo by folic acid, and entrapping Reo by the folic acid modified NKexo. The folic acid modified NKexo entrapped Reo disclosed by the invention not only can become a better conveying carrier by virtue of the anti-tumor characteristic of NKexo, but also can be combined with a folic acid receptor which is highly expressed in a tumor through folic acid, so that more Reo is protected and delivered to a tumor part, and the cancer is synergistically and jointly treated in a targeted manner.

A compound of formula Ior a pharmaceutically acceptable salt or ester thereof is provided for the treatment of cancer wherein(i) the cancer is one that has the characteristic of being a type prone to being or becoming refractory or resistant to platinum drug based therapy and(ii) the treatment is with a dose of between 1 mg / m2 and 30 mg / m2 of compound per patient body surface area per administration.Method of treatment and novel dosage forms are also provided.Particularly treated are ovarian cancers, particularly those expressing α-folate receptors, including epithelial ovarian, fallopian tube or peritoneal cancer.

The invention discloses a folate receptor mediated cell staining solution and a preparation method and application thereof, and the folate receptor mediated cell staining solution comprises the following components by weight: 0.05%-0.2% of methylene blue, 0.3%-1% of ascorbic acid, 0.3%-1% of folic acid, 1%-3% of acetic acid, 0.1%-0.4% of sodium acetate, 1%-3% of propylene glycol, 0.1%-0.5% of sodium diphenylaminesulfonate, and the balance of water. According to the sodium diphenylaminesulfonate, the cell staining solution can better distinguish different stages of tumors, so that the sensitivity and the accuracy of a detection result are ensured. In addition, the prepared staining solution is long in storage time, the detection time is shortened to a great extent, and the detection mode is simplified to a great extent.

The invention discloses a < 19 > F MRI (Magnetic Resonance Imaging) composite nano contrast agent based on a targeting artificial protein crown as well as a preparation method and application thereof. According to the invention, folic acid is modified on plasma protein, and the modified plasma protein has folic acid receptor mediated specific targeting and selective tumor cell uptake by utilizing the overexpression characteristic of a folic acid receptor (FR) on the surface of a cancer cell. Meanwhile, by taking 20-fluoro-15-crown-5-ether as a magnetic resonance active molecule, packaging by using polylactic acid-glycolic acid, and synthesizing PLGA-PFCE nano-particles as the < 19 > F MRI nano contrast agent. The PLGA-PFCE nanoparticles and the modified plasma protein are co-incubated in vitro, an artificial protein crown is formed on the surface of the PLGA-PFCE nanoparticles, and the obtained 1PLGA-PFCE nanoparticle-targeting artificial protein crown compound directly realizes targeting to tumors through targeting small molecules on the surface of the protein crown; moreover, the characteristic that the targeting effect is reduced due to the fact that a common nano material adsorbs a protein crown after entering a living body can be overcome, and the signal intensity of < 19 > F MRI tumor in-situ imaging can be improved after the nano material is enriched to the tumor through intravenous injection.

This invention discloses a fluorescent molecule targeting the folic acid receptor, its preparation method, and its applications. This invention provides a compound as shown in formula (I), its pharmaceutically acceptable salt, or its tautomer. The compound of this invention can be used as a fluorescent contrast agent in near-infrared surgical navigation.

The present invention provides a small molecule compound targeting a folate receptor, a preparation method, a composition, and a use. 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 present invention can be used as a small molecule targeted fluorescent contrast agent for adjuvant surgical treatment, and has a novel structure and good targeting performance. A near infrared fluorescence capture system provided by the present invention facilitates tumor diagnosis and treatment and has good application prospects.

Provided is a boron agent for boron neutron capture therapy, comprising a compound represented by the following formula (I) or (II):wherein C represents a carbon atom, L1, L2, L3, and L4 each independently represent a divalent group that functions as a spacer, X represents a group that binds to albumin, Y represents a group containing 10B, and Z represents a group that binds to a folate receptor.