26 results about "Tumor vessel" patented technology

The invention provides an ultrasonic activated blood coagulation targeting tumor selective prodrug as well as a preparation method and application thereof. The blood coagulation targeting tumor selective prodrug has a structure as shown in a formula I. The blood coagulation targeting tumor selective prodrug can trigger a blood coagulation cascade reaction by utilizing tumor vascular injury generated by ultrasonic induction so as to realize targeted anchoring of the drug and inhibit off-target diffusion of an active drug; meanwhile, the prodrug is activated by ultrasound, so that the limitation of tumor heterogeneity on the activation of the prodrug can be overcome. According to the technical scheme, selective enrichment of active drugs in tumors can be effectively improved, and toxicity caused by drug off-target is reduced while tumor growth is remarkably inhibited.

The invention belongs to the technical field of biotechnology and animal models, and discloses a double-person-derived mouse model for simulating a tumor immune microenvironment and a construction method and application thereof. The method comprises the following steps: firstly, pretreating NSG immunodeficient mice by adopting low-dose whole-body irradiation in combination with double-antibody targeted bone marrow depletion, and transplanting CD34 + hematopoietic stem cells from the same human donor to complete human immune system reconstruction; separating tumor primary cells, tumor-related fibroblasts and tumor vascular endothelial cells of the same donor, performing three-dimensional co-culture to obtain homologous human tumor organs, and performing in-situ inoculation to immune reconstruction mice to obtain a target model. The core defects of MHC mismatching, low immune reconstruction efficiency, poor tumor immune microenvironment simulation degree, low clinical consistency and the like of an existing model are overcome, and the method can be used for tumor immune treatment drug screening, microenvironment mechanism research and personalized tumor treatment scheme verification.

The present disclosure relates to novel adeno-associated adenovirus (AAV) vectors comprising targeting peptides. More particularly, the present disclosure relates to an adeno-associated serotype 2 virus vector, AAV2, comprising a transgene encoding LIGHT wherein the viral capsid of the AAV2 vector comprises a targeting peptide that alters its tropism to target tumor endothelial cells; and a use of the carrier. The disclosure also relates to the use of said vectors in therapy, in particular in the treatment of cancer.

The invention belongs to the technical field of biological medicine, and discloses application of THY1 in diagnosis and prognosis of glioblastoma. According to the invention, a THY1-positive cancer-related fibroblast (THY1 + CAF) subgroup is identified in glioblastoma for the first time, and it is found that the subgroup and tumor blood vessels are highly co-localized in spatial distribution, and the abundance of the subgroup and the blood vessel density are significantly positively correlated; tHY1 + CAF is a key cell component for promoting angiogenesis in a GBM tumor microenvironment; tHY1 can be used as a marker of GBM specific CAFs, and is used for auxiliary diagnosis, prognosis evaluation (high THY1 + CAF may indicate worse prognosis and stronger angiogenesis phenotype) and curative effect monitoring of GBM. Meanwhile, the target THY1 or THY1 + CAF provides a brand-new and potential action target for developing a GBM new therapy for resisting angiogenesis and even remodeling an immunosuppressive microenvironment.

The application discloses a kind of nanomedicine for tumor hypoxia, which is prepared by mPEG-SS-PLGA wrapping drug IR-1048, PFOB and 4-MU.The nanomedicine of the application is constructed by wrapping perfluorooctyl bromide (PFOB), 4-methyl umbelliferone (4-MU) and IR-1048 in tumor microenvironment-responsive amphiphilic polymer mPEG-SS-PLGA, and in response to high GSH in tumor area, 4-MU, PFOB and IR-1048 are released; 4-MU makes the dense tumor extracellular matrix loose, so that tumor vessels are normalized, which is conducive to PFOB carrying oxygen into the tumor interior, long-term solution of tumor hypoxia, remodeling of tumor microenvironment, and reduction of myeloid-derived suppressor cell (MDSC) infiltration; and under the action of 980nm laser in vitro, IR-1048 responds, and the effect of photothermal therapy of tumor is improved.

The invention provides a bispecific antibody capable of binding to PD-L1 and VEGF (vascular endothelial growth factor). The bispecific antibody comprises a first binding domain capable of binding to PD-L1 and a second binding domain capable of binding to VEGF. The bispecific antibody provided by the invention is combined with PD-L1, so that the immunosuppression of tumor cells on T cells can be relieved, and the anti-tumor function of an immune system can be recovered; meanwhile, by combining the bispecific antibody with VEGF, the growth of the tumor can be slowed down, the blood supply of the tumor can be reduced, and even the tumor blood vessel can be normalized, so that the immune environment is improved, and the attack ability of immune cells on the tumor is enhanced.

The present application belongs to the technical field of ultrasonic molecular imaging and biomedical engineering, and particularly relates to a nano-ultrasound contrast agent for enhancing immunotherapy and a preparation method and application thereof. The nano-ultrasound contrast agent for enhancing immunotherapy provided by the present application is a novel ultrasonic nano-vesicle formed by loading a protein drug for blocking an immune checkpoint into a nano-carrier with a special composition. The nano-ultrasound contrast agent has high biological safety, small and uniform particle size, can be long-circulated in vivo, has good imaging effect on the extravascular field of a tumor, has good penetration, is highly targeted, has high drug utilization rate, can improve the delivery efficiency of a tumor immunotherapy drug and the immunotherapy effect, can realize tumor diagnosis and immunotherapy integration under ultrasonic guidance, and effectively solves the current problems of difficult tumor ultrasonic diagnosis, low tumor responsiveness of an immunotherapy drug, weak targeting, and inability to be regulated in vitro.

In combination with conventional therapies (e.g., targeted therapy, chemotherapy, and angiogenesis inhibitors etc.), immunotherapies targeting checkpoint molecules have shown promise in the treatment of solid or liquid tumors. However, apoptotic regulatory T cells (Treg) induced by such therapies often become more suppressive in the tumor microenvironment (TME), through increased generation of adenosine tightly controlled by ectonucleotidases, viz. CD39 and CD73. CD39 / ENTPD1, a novel checkpoint molecule, is highly expressed and activated on the tumor vasculature and infiltrating immune cells, promoting tumor growth. Deletion or blockade of CD39 enhances anti-tumor activity by augmenting anti-tumor immune responses and inhibiting tumor angiogenesis. The present invention is based at least in part on the development of anti-CD39 antibodies which mediate CD39 downregulation on immune cells, such as T-cells with markers of T-cell exhaustion, and the demonstrated utility of these antibodies in blocking tumor growth with minimal side effects in pre-clinical models.

The invention belongs to the technical field of biomedicine, and particularly relates to a diagnosis and treatment integrated nano composite material for targeting tumor blood vessels as well as a preparation method and application of the nano composite material. The invention aims to provide the diagnosis and treatment integrated nano composite material for targeting tumor blood vessels, so that organic integration of multi-mode molecular imaging and targeted therapy is successfully realized, an innovative solution is provided for constructing a novel diagnosis and treatment integrated platform, the technical blank of existing blood vessel targeting drugs is filled, and the application prospect is wide. And meanwhile, the treatment and monitoring functions are innovatively integrated to meet the urgent clinical requirements. According to the present invention, based on the precise evaluation requirement of tumor blood vessel targeting treatment, the MRI imaging agent and the blood vessel targeting drug are grafted and integrated on the POSS through the chemical bond for the first time, such that the treatment-monitoring integration is achieved, the targeting property and the synergistic treatment effect of the nanoparticles are systematically evaluated, the pain point that the action process cannot be evaluated in real time by using the traditional drug is solved, and the application prospect is broad. And a basis is provided for clinical individualized treatment.

The invention provides an Escherichia coli outer membrane vesicle with a tumor targeting effect and a construction method thereof, and relates to the technical field of engineering transformation of Escherichia coli outer membrane vesicles. According to the invention, the tumor vascular targeting peptide GX1 is modified on the surface of the bacterial outer membrane vesicle, so that the escherichia coli outer membrane vesicle with a tumor targeting effect is successfully obtained. The escherichia coli outer membrane vesicle not only can realize a specific targeting effect on cancer cells, but also remarkably improves the problem of insufficient targeting of the tumor blood vessel targeting peptide GX1. The Escherichia coli outer membrane vesicle provided by the invention is expected to be used as a carrier for targeted delivery of antitumor drugs for further development and research.

A technology is described which provides a platform for improving the penetration into tumors in a subject of cancer treatment and cancer imaging agents for greater patient benefit. The invention in particular overcomes two challenges for use of tumor targeting methods for solid tumors: poor penetration and the immunosuppressive nature of the tumor microenvironment. The platform described here allows long-term, in vivo production of iRGD. In a preferred embodiment, CAR-T cells are engineered to secrete iRGD, a tumor-penetrating peptide to achieve tissue-penetrating delivery of drugs and imaging agents in a tumor-specific manner. The peptide acutely permeabilizes the tumor vasculature by binding to αv integrins and neuropilin, but in a tumor-specific manner. This method produces a modification in the tumor microenvironment that enhances drug access into the tumor, prevents distant metastasis of the tumor cells, and allows long-term iRGD therapy without the need for repeated injections of iRGD.

The invention relates to the technical field of biological materials, in particular to a combretastatin targeted lipid drug delivery system and a preparation method thereof. According to the method, AS1411 and ApoE peptides are adopted to carry out joint modification on CA4 / HM-Fe lipidosome. Fe < 3 + > is introduced on the basis of the sound-sensitive agent HMME, so that the sound-sensitive agent HMME and the sound-sensitive agent HMME are self-assembled to form an HM-Fe complex, CA4 and free HMME are entrapped in a hydrophobic region, and HM-Fe is entrapped in a hydrophilic core, so that the HM-Fe complex can be used as a good carrier for delivering CA4, and the problem of poor water solubility of CA4 is effectively solved. The liposome is co-modified by AS1411 and ApoE peptide, so that dual active targeting of liver cancer cells and tumor vascular endothelial cells can be realized, the in-vitro uptake efficiency is effectively improved, and the enrichment efficiency of a drug at a tumor part is remarkably improved; the system is high in stability, low in toxicity, efficient, good in biocompatibility, high in tumor inhibition rate and good in tumor inhibition effect and safety.

The invention discloses a medical image automatic positioning system based on deep learning, which comprises an image preprocessing module, a feature extraction module, a positioning optimization module and a post-processing module, and is characterized in that multi-level spatial features are extracted by constructing a five-layer multi-scale feature pyramid network, and accurate positioning is realized by adopting a three-level cascade attention mechanism; and finally, a positioning result is optimized through a self-adaptive post-processing algorithm. According to the invention, a space and channel dual attention mechanism is innovatively designed, so that the positioning precision Dice coefficient reaches 0.92 + / -0.03, and the positioning precision is improved by more than 40%. The system is particularly suitable for positioning key parts such as tumors and vasculopathy, and reliable technical support is provided for precise medical treatment.

The invention belongs to the technical field of biomedicine, and provides a breast pad in-situ tumor animal model blood flow velocity prediction method for solving the problem that an existing solid tumor blood flow velocity detection method is difficult to be widely applied to conventional research, and the method comprises the steps that the blood flow velocity and the tumor volume of in-situ tumor blood vessels are continuously collected; analyzing the animal plasma sample to obtain the plasma cell factor concentration related to the blood vessel function; and fitting the morphological characteristics of the tumor tissue, the cell factor concentration and the blood flow velocity of the tumor blood vessel to construct a blood flow velocity prediction model based on the tumor volume and a blood flow velocity prediction model based on the plasma cell factor concentration. Through the constructed prediction model, a researcher can conveniently predict the blood flow velocity of the tumor blood vessel through the obtained data only by obtaining tumor volume data or concentration data of a certain plasma cell factor, additional animal experiments are not needed for measurement, and the method can be widely applied to conventional research.

The invention discloses a tumor treatment system based on an ultrasonic fatigue effect, which directly damages a cancer cell membrane structure and destroys the integrity of the cancer cell membrane structure through the continuous action of low-intensity ultrasonic energy, specifically targets a disordered tumor extracellular matrix by utilizing the ultrasonic fatigue effect, and simultaneously causes mechanical damage to tumor blood vessels. The tumor core hypoxia caused by nutrition delivery is blocked, so that cell apoptosis is induced. And the multi-layer mechanical-biological effect jointly inhibits tumor growth. The tumor treatment system is combined with temozolomide for use, can synergistically amplify the anti-tumor effect, and is suitable for hypoxic tumors tolerated by a traditional therapy. According to the treatment system, a non-invasive and controllable tumor treatment mode is achieved through accurate regulation and control of energy, and a new thought is provided for tumor treatment.

The invention discloses an application of an AZD2858 compound in preparation of a synergist of a chemotherapeutic drug for brain glioma. The invention discloses application of an AZD2858 compound in preparation of a reagent or a medicine for inducing tumor vessel normalization. The invention further discloses a pharmaceutical composition for treating brain glioma. The pharmaceutical composition comprises the AZD2858 compound and a brain glioma chemotherapy drug. The AZD2858 compound disclosed by the invention can induce tumor blood vessel normalization so as to improve the delivery and effect of the brain glioma chemotherapeutic drug, and the problems that the current brain glioma chemotherapeutic drug is poor in treatment effect and delivery effect are solved.

The application relates to the field of biotechnology, in particular to a nanobody targeting annexin A1 and a preparation method and application thereof, discloses a nanobody targeting annexin A1, the nanobody comprises a nanobody Nb6, wherein the amino acid sequence of the nanobody Nb6 is shown in Seq.ID NO.1, the nanobody Nb4 provided has higher affinity with annexin A1, the nanobody can be used for targeted action on annexin A1, has high-strength combination capacity with annexin A1, is favorable for development of a nanobody related medicine of annexin A1, realizes targeted treatment and imaging of tumors, and has very great clinical application value. Meanwhile, a molecular probe can be prepared based on the nanobody, the molecular probe is specifically combined with a tumor blood vessel surface annexin antigen, is applied to specific imaging and diagnosis of tumors, and is used for delivery of related medicines, and is widely applied.

The invention relates to the field of biological medicine, in particular to a compound, a P4HA1 competitive antagonist and application of the P4HA1 competitive antagonist in tumor treatment. The invention provides a compound with a structure as shown in a formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, or a raceme thereof. The invention also provides application of the compound in preparation of a P4HA1 competitive antagonist and in preparation of a product for preventing and / or treating diseases related to P4HA1 or downstream signal factors thereof. The invention designs and synthesizes a compound which can be used as a small-molecule competitive antagonist of P4HA1, and can reduce the succinic acid level of cells, inhibit phosphorylation and glycolysis of an S203 site of PGK1 in tumor cells, inhibit an E2F1-DNA damage repair axis and reduce high expression of VEGFA in tumor blood vessels.

The invention discloses a tumor blood vessel blocking type light diagnosis and treatment reagent and a preparation method thereof.The preparation method comprises the steps that in the nitrogen atmosphere, aza-BODIPY molecules NBDP and a blood vessel blocking reagent 5, 6-dimethylxanthine-4-acetic acid are dissolved in a dichloromethane medium; the light diagnosis and treatment molecule NVDA is obtained through a reaction by taking NVDA as a substrate, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide) as a carboxyl activating reagent and 4-dimethylaminopyridine as a reaction catalyst. The optical diagnosis and treatment reagent NVDA nano-particles can selectively destroy tumor blood vessels and realize high-resolution blood vessel NIR-II fluorescence imaging so as to dynamically monitor the damage process of the tumor blood vessels; under the irradiation of 808 nm laser, the NVDA nanoparticles can efficiently generate I-type active oxygen species, and also show the photothermal conversion efficiency as high as 44%; the NIR-II fluorescent imaging-mediated I-type photodynamic therapy, photothermal therapy and vascular disruption combined therapy for deep tumor tissues can be used for efficiently killing tumor cells.

The invention belongs to the technical field of medicines, and discloses a liposome for resisting angiogenesis and down-regulating PD-L1 protein as well as a preparation method and application of the liposome. According to the invention, the active targeting liposome which is modified by NGR and is co-loaded with axitinib and siRNAPD-L1 is prepared by a film dispersion method and a lipid co-extrusion method. The method is simple in preparation process, low in cost, good in stability and high in repeatability. On one hand, Axi / siRNAPD-L1-coated NGR-Lipo inhibits tumor microangiogenesis, reshapes a tumor vascular system, normalizes tumor vessels, inhibits tumor metastasis and improves a tumor immunosuppression microenvironment; on the other hand, PD-L1 protein on the surfaces of tumor cells is silenced, tumor immune escape is relieved, and tumor immunotherapy is enhanced. The Axi / siRNAPD-L1 coated NGR-Lipo realizes an enhanced anti-tumor effect by combining an anti-angiogenesis therapy and an immune checkpoint blocking therapy. The preparation process of the liposome is simple and rapid, is easy for large-scale and industrial production, and also has a better development prospect in the aspect of clinical application transformation.

The invention provides new materials and associated methods that are designed to address certain complex biological phenomena associated with pathologies such as cancer. In this context, embodiments of the invention disclosed herein can provide a multimodal, multitemporal approach to cancer therapy by, for example, targeting selected tumor vessels using materials designed deliver antineoplastic agents as well as anti-angiogenic agents, immunotherapeutic agents, and / or imaging agents, in a temporally controlled fashion.

The present invention relates to a computer-implemented method capable of automatically classifying and differentiating biliary lesions in images obtained from a digital cholangioscopy system, characterizing them according to their malignant potential, through the classification of pixels as a malignant lesion, or benign lesion, followed by a characterization stage and indexing of such lesions according to a set of morphologic characteristics with clinical relevance, namely the presence / absence of tumor vessels, the presence / absence of papillary projections, the presence / absence of intraductal nodules and the presence / absence of tumor masses.

The invention discloses an application of a radioactive polyethylene resin microsphere as an anti-tumor drug, the radioactive polyethylene resin microsphere is a 90Y carboxylic acid type polystyrene resin microsphere (90Y-SPS) modified with streptavidin, and the radioactive polyethylene resin microsphere is used as follows: the 90Y-SPS and 68Ga-biotin are combined for use, Ga-biotin is injected 12-24 hours after the 90Y-SPS microsphere is injected, and the radioactive polyethylene resin microsphere is used as an anti-tumor drug. Injected < 68 > Ga-biotin is combined with streptavidin on the < 90 > Y-SPS microspheres in blood vessels for imaging, so that distribution of < 90 > Y-SPS in tumor blood vessels is visually monitored, and integration of tumor diagnosis and treatment is realized.

The application belongs to the technical field of biological medicine, and discloses a tumor local acute inflammation inducer, a preparation method and application thereof. Specifically, extracted bacterial outer membrane vesicles are loaded into prepared temperature-sensitive hydrogel for in-situ injection treatment of common clinical solid tumors, such as breast cancer, melanoma, colorectal cancer and the like. The temperature-sensitive hydrogel loaded with bacterial outer membrane vesicles constructed in the application induces acute inflammation at the tumor site, effectively activates anti-tumor immunity, and improves the immunosuppressive microenvironment; at the same time, the temperature-sensitive hydrogel causes rupture of tumor blood vessels, and can be combined with photothermal therapy to further eradicate tumors; and the temperature-sensitive hydrogel limits acute inflammation in the tumor, improves biological safety, and provides a new strategy for development of in-situ tumor treatment preparations.

The invention discloses a self-gelation temperature-sensitive gelatin embolization microsphere and a preparation method and application thereof.The gelatin microsphere is crosslinked through tannic acid to form a unique structure with the surface highly crosslinked and the interior lightly crosslinked, so that the gelatin microsphere can be independently dispersed at the room temperature after being rehydrated and can be mutually fused to be self-gelated after being delivered into the body, and the self-gelation temperature-sensitive gelatin embolization microsphere has the advantages that the self-gelation temperature-sensitive gelatin embolization microsphere is formed; therefore, the original gaps among the microspheres are filled, and the embolism effect is improved. Meanwhile, the temperature-sensitive gelatin microspheres have densified surfaces and can encapsulate contrast agents or drugs in advance, so that the effect of long-acting development or drug sustained release is achieved. In addition, the gel formed after fusion of the temperature-sensitive gelatin microspheres has tissue adhesion, can effectively avoid displacement of the gel, eliminates gaps between the microspheres and the blood vessel wall, and further improves the embolism effect. The temperature-sensitive gelatin microspheres can be applied to interventional embolism treatment in the fields of tumors, vascular deformity, arthralgia and the like.

The present application relates to the technical field of biological medicine, and particularly relates to application of SHLA in preparation of a glioblastoma chemotherapy sensitizer.SHLA is a high-affinity leptin antagonist, which can block the JAK / STAT3, p38-MAPK and other signal pathways mediated by leptin.In a human GBM cell line orthotopic xenograft mouse model, under the premise of not affecting tumor vascular endothelial cells, SHLA significantly reduces the coverage of tumor pericytes, thereby destroying the "blood-tumor barrier" of glioblastoma and increasing the permeability of the "blood-tumor barrier", and improving the concentration of chemotherapeutic drugs in tumor tissues, thereby playing a chemotherapy sensitization role.SHLA has no serious side effects on non-targeted main organs, has no effect on the "blood-brain barrier", and has good safety.