32 results about "Radiosensitizer" patented technology

The present application relates to a kind of radiotherapy sensitization microneedle and its preparation method and application, belong to biological medicine technical field.The radiotherapy sensitization microneedle of the present application includes hyaluronic acid and nano radiosensitizer;The radiotherapy sensitization microneedle is obtained by drying after hyaluronic acid and nano radiosensitizer solution are mixed;The nano radiosensitizer solution is prepared by the following method: hafnium salt, 1,1'-ferrocene dicarboxylic acid and benzoic acid are mixed in organic solvent and stirred, centrifugal;The supernatant obtained is dialyzed, extracted, and the liquid phase obtained after solid-liquid separation is nano radiosensitizer solution.The radiotherapy sensitization microneedle of the present application is applied to the growth inhibition and radiotherapy sensitization of mouse melanoma cell B16F10 cell, can fully play the role of radiotherapy sensitization while overcoming the limitation of prior art, and preparation route is simple, and have certain conversion prospect.

The application of poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers in constructing micro / nanocarriers for antitumor drugs belongs to the field of biomedical polymer materials and nanomedicine. The antitumor drugs are small-molecule chemotherapeutic agents, small-molecule photosensitizers, small-molecule immunotherapeutic agents, and small-molecule radiosensitizers. The particle size of the poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers is 10–5000 nm. The effective concentration of the poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers is 1–500 mg / kg. The antitumor mechanism of the poly(D-lactic acid) and poly(D-lactic acid-glycolic acid) copolymers includes increasing the activity of effector T cells in the tumor microenvironment and increasing the concentration of cytokines such as IFN-γ at the tumor site. In the field of tumor therapy, PLA and PLGA materials composed of D-lactic acid have shown good effects in inhibiting tumor growth, prolonging the survival period of tumor-bearing mice, and activating antitumor immune responses.

The invention belongs to the field of biological medicine, and particularly relates to a high-selectivity sensitizer for solid tumor radiotherapy and a preparation method thereof.The sensitizer comprises two newly-designed modified compounds: a derivative based on a diamino-anthraquinone structure and capable of enhancing radiation energy deposition and relieving tumor hypoxia; and the other one is a cystamine derivative containing a diselenide bond, and can effectively consume overexpressed glutathione in tumor cells and enhance the generation of active oxygen. The preparation method comprises the following steps: dissolving the two modified compounds and the biodegradable polymer in an organic solvent to form an organic phase, dissolving phospholipid polyethylene glycol amino in warm water, blending with a stabilizer in a buffer solution to form a water phase, dropwise adding the organic phase into the water phase through a nano-precipitation method, self-assembling to form nano-particles, and filtering and purifying to obtain a final product. The sensitizer can specifically target tumor tissues, the radiotherapy effect is remarkably improved through a multiple synergistic mechanism, meanwhile, the damage to normal tissues is reduced, the preparation process is simple and convenient, and the reproducibility is good.

Systems and methods for radiation therapy for cancerous tumors using biocompatible quantum dots to provide radiation dose enhancement and resistance to metastasis are described. In an aspect, a method for radiation therapy treatment of cancer cells, includes, but is not limited to, preparing a radiosensitizer fluid, the radiosensitizer fluid including a plurality of biocompatible quantum dots; introducing the radiosensitizer fluid to cancer cells; and irradiating the cancer cells with the radiosensitizer fluid to promote generation of reactive oxygen species and inhibit radiation-induced enhancement of cell-migration.

Disclosed herein is a radio-afterglow nanoparticle (RANP) comprising ABCD, wherein: A represents a radioabsorber; B represents a radiosensitizer; C represents a luminescent component; and D represents an amphiphilic polymeric matrix. Also disclosed herein are a method for the detection of cancer in vivo, a method of treating cancer, a method of treating cancer in a patient by administering the aforementioned radio-afterglow nanoparticle, uses of the aforementioned radio-afterglow nanoparticle, and a drug comprising the aforementioned radio-afterglow nanoparticle.

The invention relates to an application of suramine in promoting tumor radiotherapy sensitization. The invention fully proves that suramin can effectively prepare tumor cells in a state highly sensitive to ferroptosis through a novel metabolic reprogramming mechanism of inhibiting IPPK, reducing IP6 and releasing Fe < 2 + > chelated with an iron pool in cells, thereby creating necessary biochemical conditions for ferroptosis; and the sensitivity of cells to ferroptosis induced stimulation is fundamentally changed. Therefore, the compound can be used as a ferroptosis inducer and a potent sensitizer for radiotherapy at the same time. The discovery not only provides a new combined strategy for overcoming tumor treatment resistance, but also perfectly explains the transformation medicine concept of new use of old medicines, and provides a new active ingredient for human tumor treatment, thereby providing a new direction for subsequent medicine research and development, clinical treatment and the like, and having extremely high social value and market application prospects.

The application provides a preparation method of selenium-doped Prussian blue nanoparticles modified by a targeting polypeptide, and comprises the following steps: (1) synthesizing Prussian blue nanoparticles by a microwave method; (2) synthesizing selenium-containing Prussian blue by a gas-phase atomic deposition method; and (3) preparing selenium-doped Prussian blue nanoparticles modified by a targeting polypeptide: dissolving a tumor-targeting RGD cyclic peptide in ultrapure water, adding a catalyst N-hydroxysuccinimide and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and then stirring, then performing dialysis, adding the selenium-containing Prussian blue into the dialysate, stirring, centrifuging, resuspending and obtaining the selenium-doped Prussian blue nanoparticles modified by the targeting polypeptide. According to the preparation method, the selenium is naturally deposited on the surface of the Prussian blue by the gas-phase atomic deposition method, monodisperse selenium with controllable doping amount is formed, and the selenium-doped Prussian blue modified by the targeting polypeptide is prepared.

The subject of the application is a 2'-deoxyadenosine derivative in the form of 8-(4-trifluorothio)benzylamino-2'-deoxyadenosine of formula 1 and its use as a radiosensitizer of DNA damage, which sensitizes cancer cells to ionizing radiation. The application also covers a method for obtaining 8-(4-trifluorothio)benzylamino-2'-deoxyadenosine of formula 1, characterized in that 8-bromo-2'-deoxyadenosine of formula 2 is mixed with 4-trifluorothiobenzylamine of formula 3 in a molar ratio of 1:8, in the presence of methanol, and then the mixture is heated to reflux and stirred for 72 h.

The present invention relates to an inhibitor of intracellular copper-zinc superoxide dismutase for use in protecting subjects from radiation burst injury. The present invention also relates to a kit comprising an SOD1 inhibitor and a radiosensitizer for cancer cells, the in vitro use of an SOD1 inhibitor for protecting non-cancer cells from ionizing radiation, and methods, compositions, and uses relating thereto.

The invention belongs to the technical field of biological catalytic materials, and particularly relates to a gold monatomic radiosensitizer with multienzyme activity as well as a preparation method and application of the gold monatomic radiosensitizer. The gold monatomic radiosensitizer is a coordination complex formed by a gold source containing tetrachloro gold (III) acid radical ions and 2, 4, 6-tri (4-pyridyl)-1, 3, 5-triazine through a coordination substitution reaction of Au and pyridine nitrogen. The gold monatomic radiosensitizer disclosed by the invention is a biocatalyst which is newly designed, has multi-enzyme activity biological catalysis performance and can be activated by radiation, and can be used as a polymer artificial enzyme for efficient and controllable tumor treatment.

Radiosensitizer prodrugs and formulations and methods of use thereof are provided. Typically, the radiosensitizer prodrug is an analog of a radiosensitizer parent compound having one or more S-nitrosothiol moieties. Typically, the S—N bond of the S-nitrosothiol moiety can be cleaved by radiation during radiotherapy, releasing the parent compound and nitric oxide. One or preferably both the parent compound and the nitric oxide can contribute to death of tumor cells exposed to radiotherapy. Nanoparticle formulations for delivery of the prodrug, and methods of using them in combination with radiotherapy to treat tumors and cancer are also provided.

Conjugates of the formula T-L-A wherein T is a ligand targeting prostate specific membrane antigen (PSMA), L is a linker, and A is a radiosensitizer; a pharmaceutical composition comprising the conjugate and a pharmaceutically acceptable carrier; and methods of treating prostate cancer or metastases thereof in a patient using radiotherapy. A conjugate of formula T-L-A can be administered prior to or after administration of a conjugate of formula T-L-X, wherein X is or comprises a radiotherapy or (radiation) imaging agent. Conjugates of formula T-L-(X) A, pharmaceutical compositions comprising the same, and methods of use are also disclosed.

The invention discloses application of USP15 in preparation of a bladder cancer radiotherapy sensitizer, and belongs to the technical field of biological medicine. The objective of the invention is to improve the radiotherapy sensitivity of bladder cancer. The invention relates to an application of USP15 in preparation of a bladder cancer radiotherapy sensitizer. The USP15 is used for preparing the bladder cancer radiotherapy sensitizer. The radiotherapy sensitivity of the bladder cancer is improved by overexpressing the USP15. The USP15 can regulate and control the stability of FIS1 protein through ubiquitination modification so as to inhibit the mitochondrial function, and the activation of the regulation and control pathway is the core mechanism of the USP15 for exerting the radiotherapy sensitization effect. In conclusion, the invention not only provides a new thought for molecular mechanism research of bladder cancer radiotherapy sensitization, but also provides a potential strategy for treatment of clinical radiotherapy resistant bladder cancer patients, and has important drug development value and clinical application prospect.

This invention discloses the application of disulfiram or its pharmaceutical salt in the preparation of radiosensitizers, wherein the radiosensitizer refers to a radiosensitizer for malignant tumors, specifically osteosarcoma. The radiation involved in the radiosensitizer is selected from alpha, beta, gamma, or X-ray radiation. This invention is the first to discover and confirm a novel use of disulfiram in enhancing the radiosensitivity of malignant tumors, significantly inhibiting the proliferation of osteosarcoma cells after radiotherapy and promoting cell death in vitro. It also demonstrates outstanding efficacy in inhibiting the growth of subcutaneously implanted osteosarcoma in mice after radiotherapy.

The present invention provides a radiosensitizer or anti-cancer chemotherapy sensitizer including a combination of (a) hydrogen peroxide and (b) hyaluronic acid or a salt thereof, wherein the hydrogen peroxide content in a final formulation is 0.1 to 3.5 weight percent.

The invention addresses radioresistance in cancer treatment involving radiotherapy and, in particular, limitations associated with the use of the drug sulfasalazine. Specifically, it provides a series of compounds for use as radiosensitizers in the treatment of cancers such as glioblastomas which are lethal and inherently resistant to radiotherapy. In one embodiment, the invention provides compounds of general formula (I), their stereoisomers and pharmaceutically acceptable salts for use as radiosensitizers in the treatment of cancer:wherein ring A is selected from optionally substituted phenyl, biphenyl and fluorenyl; each X is independently selected from: —C1-6 alkyl (preferably C1-3 alkyl, e.g. —CH3), —O—C1-6 alkyl (preferably —O—C1-3 alkyl, e.g. —OCH3), —S—C1-6 alkyl (preferably —S—C1-3 alkyl, e.g. —SCH3), —OH, —SH, —CO2R1 (where R1 is H or C1-6 alkyl, preferably C1-3 alkyl, e.g. —CH3), —SO2—C1-6 alkyl (preferably —SO2—C1-3 alkyl, e.g. —SO2—CH3), —SO2—NR2R3 (where R2 is H and R3 is optionally substituted phenyl), —NR4R5 (wherein R4 and R5 are independently selected from H, C1-6 alkyl (preferably C1-3 alkyl, e.g. —CH3), and —CO—C1-6 alkyl (preferably —CO—C1-3 alkyl, e.g. —CO—CH3), halogen (e.g. F, Cl or Br), and optionally substituted tetrazolyl; n is an integer from 0 to 5, preferably 0 to 2, e.g. 1 or 2; and denotes an E or Z double bond.

Compounds and pharmaceutically acceptable salts thereof of Formula (I) are disclosed. Certain compounds and salts of Formula (I) are active as TDP1 inhibitors and radiosensitizers of cancer cells. The disclosure provides pharmaceutical compositions containing a compound of Formula (I) as the only active agent, or optionally containing one or more additional active agents. Methods of using compounds of Formula (I) to treat a cancer are provided in this disclosure. The disclosed compounds of Formula (I) may be used alone to treat cancer, but may also be used in combination with another active agent, such as a TOPI inhibitor, for example, camptothecin or a camptothecin analogue, and / or ionizing radiation.

The invention relates to the technical field of biological medicines, and particularly discloses application of a PPAR pathway regulator in preparation of a nasopharyngeal carcinoma radiotherapy sensitizer. In-vitro experiments prove that after the expression of the MAP2K7 gene in nasopharynx cancer cells is silenced by utilizing shRNA, the sensitivity of the cancer cells to radioactive rays can be remarkably enhanced. Mechanism research is carried out by using a transcriptome sequencing technology, it is found that MAP2K7 silently up-regulates the activity of a PPAR pathway, that is, MAP2K7 influences the radiotherapy sensitivity by regulating a PPAR signal pathway, and the activity of the PPAR pathway is in positive correlation with the radiotherapy sensitivity of nasopharyngeal carcinoma. The invention provides a new therapeutic target and a solution for nasopharyngeal carcinoma radiotherapy resistance, and lays a theoretical basis and an experimental basis for developing a novel radiotherapy sensitizer based on an MAP2K7-PPAR pathway.

The invention relates to a radiotherapy sensitization microneedle and a preparation method and application thereof, and belongs to the technical field of biological medicine. The radiotherapy sensitization microneedle provided by the invention comprises hyaluronic acid and a nano radiosensitizer, the radiotherapy sensitization microneedle is obtained by mixing hyaluronic acid and a nano radiosensitizer solution and then drying; the nano radiosensitizer solution is prepared by the following steps: mixing hafnium salt, 1, 1 '-ferrocene dicarboxylic acid and benzoic acid in an organic solvent, stirring, and centrifuging; and dialyzing and extracting the obtained supernate, and carrying out solid-liquid separation to obtain a liquid phase which is a nano radiosensitizer solution. The radiotherapy sensitization microneedle is applied to growth inhibition and radiotherapy sensitization of mouse melanoma cells B16F10, the radiotherapy sensitization effect can be brought into full play, meanwhile, the limitation of the prior art is overcome, the preparation route is simple, and the radiotherapy sensitization microneedle has a certain conversion prospect.

Compounds and pharmaceutically acceptable salts thereof of Formula (I) are disclosed. Certain compounds and salts of Formula (I) are active as TDP1 inhibitors and radiosensitizers of cancer cells. The disclosure provides pharmaceutical compositions containing a compound of Formula (I) as the only active agent, or optionally containing one or more additional active agents. Methods of using compounds of Formula (I) to treat a cancer are provided in this disclosure. The disclosed compounds of Formula (I) may be used alone to treat cancer, but may also be used in combination with another active agent, such as a TOPI inhibitor, for example, camptothecin or a camptothecin analogue, and / or ionizing radiation.

The application belongs to the technical field of biological catalytic materials, and particularly relates to a gold monatomic radiosensitizer with multiple enzyme activities and a preparation method and application thereof. The gold monatomic radiosensitizer is a coordination complex formed by a coordination substitution reaction of a gold source containing a tetrachlorogold (III) acid radical ion and 2,4,6-tris (4-pyridyl) -1,3,5-triazine through Au and pyridine nitrogen. The gold monatomic radiosensitizer disclosed in the application is a newly designed biological catalyst with multiple enzyme activities and radioactivation, and can be used as a polymer artificial enzyme for efficient and controllable tumor treatment.

Radiosensitizer prodrugs and formulations and methods of use thereof are provided. Typically, the radiosensitizer prodrug is an analog of a radiosensitizer parent compound having one or more S-nitrosothiol moieties. Typically, the S—N bond of the S-nitrosothiol moiety can be cleaved by radiation during radiotherapy, releasing the parent compound and nitric oxide. One or preferably both the parent compound and the nitric oxide can contribute to death of tumor cells exposed to radiotherapy. Nanoparticle formulations for delivery of the prodrug, and methods of using them in combination with radiotherapy to treat tumors and cancer are also provided.

The present application relates to the technical field of radiotherapy and chemotherapy sensitizers, and particularly relates to application of a preparation with EMILIN1 gene inhibition in preparation of a radiotherapy and chemotherapy sensitizer. Based on deep research on the tumor microenvironment and tumor-related fibroblasts of colorectal cancer, it is found that EMILIN-1 is significantly up-regulated in patients with radiotherapy and chemotherapy resistance. By designing siRNA to specifically inhibit the expression of EMILIN1 gene, the radiotherapy and chemotherapy sensitivity of colorectal cancer can be effectively improved. The present application provides a variety of application forms such as cholesterol-modified siRNA and tumor-related fibroblasts transfected with siRNA, which significantly improve the sensitivity of colorectal cancer cells to radiotherapy and chemotherapy drugs. The technical scheme can solve the technical problem that there is no means to effectively inhibit the radiotherapy and chemotherapy resistance of colorectal cancer cells in the prior art, and provides multiple options for clinical transformation, and has good development and application prospect.

The application belongs to the technical field of biological medicine, and particularly relates to application of a small molecule interfering with HK2-RUVBL2 protein interaction in preparation of an anti-tumor drug. The application targets and regulates the interaction between metabolic enzyme hexokinase 2 (Hexokinase 2, HK2) and RUVBL2 protein, affects the transcription of the key regulation axis-PIKK (Phosphatidylinositol 3-kinase-related kinases) family protein of DNA damage response (DNA Damage Response, DDR), thereby significantly changing the sensitivity of tumor cells to radiotherapy, and then the small molecule interfering with HK2-RUVBL2 protein interaction can be used as a radiosensitizer to achieve the anti-tumor effect, has the radiosensitization characteristics of precision and low toxicity, and has good clinical transformation potential.

This application belongs to the field of radiosensitizer technology, and particularly relates to a radiosensitizer that enhances radiation deposition ability and dispersion stability, as well as its preparation method and formulation. The radiosensitizer provided in this application is prepared by ball milling, avoiding the defects of traditional hydrothermal synthesis radiosensitizers, such as poor particle size and dispersibility between different batches and lack of environmental friendliness. At the same time, physical pulverization and chemical / physical modification are simultaneously achieved during ball milling, obtaining a radiosensitizer with enhanced radiation deposition ability and dispersion stability in one step. Furthermore, by improving processes such as ball milling speed, a radiosensitizer with further enhanced radiation deposition ability can be obtained. Thus, it solves the technical problem that the radiation deposition ability and dispersion stability of hafnium oxide nanoparticles in the prior art are low, making it difficult to meet the performance requirements of radiosensitizers.

The invention discloses a human cervical cancer radiotherapy resistant cell strain as well as a construction method and application thereof, and belongs to the technical field of tumor radiation biology. In order to solve the technical bottlenecks of clinical disjunction, phenotype instability and single evaluation system of an existing cervical cancer cell radiation resistance model, progressive accumulative irradiation (40 times * 2Gy, the total dose is 80Gy) is performed on human cervical cancer ME180 cells, a clinical radical radiotherapy process is simulated, and a cervical cancer radiation-tolerant strain ME180-R is constructed. In the method, a maintenance irradiation strategy of 2Gy per week is innovatively introduced, so that the radiation resistance phenotype of the cell strain can be stably passed for at least 10 generations. According to the method, a quantitative evaluation system containing multi-dimensional parameters such as D0, Dq and SF2 is established at the same time. The cell strain and the construction method thereof provide reliable and stable preclinical models and tools for transformation medical research such as cervical cancer radiotherapy sensitizer screening, radiation resistance mechanism analysis, individualized radiotherapy scheme optimization and the like.

This invention belongs to the field of biomedical technology, specifically relating to a gadolinium-based radiosensitizer that specifically targets ferritin, its preparation method, and its application. The gadolinium-based radiosensitizer that specifically targets ferritin has the structure shown in Formula (I): Formula (I). The gadolinium-based radiosensitizer prepared by this invention achieves precise enrichment in tumor tissues through biotin-mediated active targeting, and significantly reduces non-specific distribution in normal tissues, thereby improving treatment safety. After entering tumor cells, its targeting ligand can specifically bind to highly expressed ferritin, achieving precise intracellular anchoring and secondary enrichment. Under X-ray irradiation, the gadolinium core exerts a radiosensitizing effect, enhancing ROS production and destroying ferritin at close range, effectively enhancing the killing efficacy of radiotherapy on tumor cells, and effectively inhibiting the survival and proliferation of tumor cells after radiotherapy, achieving the dual goals of enhancing efficacy and reducing toxic side effects.

This invention discloses an absorbable particle cannula loaded with dual radiosensitizers, designed to effectively enhance the efficacy of internal irradiation radiotherapy while facilitating the implantation of radioactive particles. The entire material is biodegradable and absorbable within the body, eliminating the need for secondary surgery. The absorbable particle cannula mainly comprises a cannula body for encapsulating radioactive particles, spacers within the cannula body for separating the radioactive particles, and a polydopamine coating loaded with dual radiosensitizers consisting of metal nanoparticles and an aromatic ring-structured drug. In the polydopamine coating, the metal nanoparticles are formed by the in-situ reduction of metal ions onto the coating surface via the catechol groups of polydopamine; while the drug is loaded onto the coating surface through non-covalent interactions (π-π stacking, hydrophobic interactions, and / or electrostatic attraction).

This invention discloses a nano-heterojunction radiosensitizer suitable for hypoxic tumors and its preparation method. The radiosensitizer is a core-shell structured nanoparticle, comprising a core and a shell. The core is a high-valence bismuth-based nanomaterial, including at least one of sodium bismuthate, silver bismuthate, and potassium bismuthate. The shell coats the surface of the core and comprises a metal oxide. A Z-shaped heterojunction is formed between the inner core and the outer shell. Under X-ray excitation, this heterojunction forms a built-in electric field, promoting electron-hole separation. Electrons in the high-valence bismuth nanoparticle phase reduce high-valence bismuth (Bi). 5+ →Bi 3+ ) and releases highly reactive lattice oxygen, which then reacts with holes on the TiO2 phase to generate singlet oxygen ( 1 O2), while the holes on TiO2 oxidize water molecules to produce hydroxyl radicals (•OH).