83 results about "Tumor microenvironment" patented technology

The invention provides preparation of ROS responsive lipidosome and application of the ROS responsive lipidosome in anti-pancreatic cancer drugs, and belongs to the technical field of ROS responsive lipidosome preparation. The liposome can synergistically deliver formononetin and salvianolic acid B, overcomes the defects of formononetin and salvianolic acid B in the aspects of solubility, stability and bioavailability, and improves the curative effect of formononetin and salvianolic acid B in pancreatic cancer treatment. The ROS-responsive formononetin liposome and the salvianolic acid B liposome are wrapped by the cell-derived nano-vesicles through co-extrusion with the nano-vesicles on the outer layer, so that the ROS-responsive liposome is prepared. The liposome can be used for preparing anti-pancreatic cancer drugs, realizes targeted treatment of pancreatic cancer, inhibition of pancreatic cancer cell proliferation, promotion of pancreatic cancer cell apoptosis and improvement of pancreatic cancer tumor microenvironment energy metabolism disorder, and has the advantages of high biological safety, controllable drug release and the like.

The invention provides an organoid chip for screening micro-ecological drugs as well as application and a preparation method of the organoid chip, and relates to the technical field of biological medicines. The invention provides a chip integrating intestinal epithelium, a prostate cancer organ and a bladder cancer organ, which is used for researching how microecological preparations, such as probiotics, metabolites and the like, affect tumor microenvironment and immunotherapy effects. The chip can simulate interaction of intestinal tract-tumor axis, and provides an in-vitro evaluation system for precise tumor immunotherapy.

The invention discloses a functionalized culture medium, a culture medium composition and a culture method for NK cell amplification, and belongs to the field of biological medicine. Aiming at the problem that the activity and the purity of the NK cells cannot be considered at the same time in the existing NK cell in-vitro amplification, the invention provides a functionalized culture medium for NK cell amplification, and the functionalized culture medium comprises a proliferation culture medium and an activation adaptation culture medium; the proliferation culture medium and the activated adaptive culture medium both comprise IL-10, and the concentration of the IL-10 in the proliferation culture medium is lower than that of the IL-10 in the activated adaptive culture medium. IL-10 is added into a proliferation culture medium and an activation adaptation culture medium, the concentration of IL-10 in the two culture mediums is different, and the synergistic effect of high purity (larger than 95%) and high activity (the killing rate is larger than 75%) is achieved by inhibiting T cell proliferation and enhancing the anti-tumor microenvironment capacity of NK cells.

The invention discloses a preparation method of oxygen deficit and H2O2 dual-response COF nano-enzyme and application of the oxygen deficit and H2O2 dual-response COF nano-enzyme in treatment of pancreatic cancer, and belongs to the technical field of application materials. The COF is prepared from 1, 3, 6, 8-tetra (4-formylphenyl) pyrene (Py-CHO), p-diaminoazobenzene (Azo-NH2), ferroferric oxide (Fe3O4), dopamine hydrochloride (DA) and hyaluronic acid (HA), and the COF is prepared from the following raw materials in parts by weight: 1, 3, 6, 8-tetra (4-formylphenyl) pyrene (Py-CHO), p-diaminoazobenzene (Azo-NH2), ferroferric oxide ( Under a tumor microenvironment (TME), the CFPH can be split due to reductase existing in an anoxic environment, released Fe3O4 can react with H2O2 in TME to generate ROS, and pancreatic cancer cells are effectively killed. The COF prepared by the invention is low in cost, simple and convenient in preparation method and good in biocompatibility, and has a wide application prospect in the aspect of pancreatic cancer treatment.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.

This invention discloses a composite nanodelivery system encapsulated in a fusion membrane, its preparation method, and its applications. The nanodelivery system comprises a Ti3C2 / TiO2 / CuInS2 composite material, oxaliplatin loaded thereon, and a fusion membrane encapsulating the outer layer; the fusion membrane is formed by the fusion of Fusobacterium nucleatum extravesicles and M1 macrophage membranes. This invention also discloses a method for preparing the nanodelivery system, including the steps of preparing the Ti3C2 / TiO2 / CuInS2 composite material, preparing the fusion membrane, loading oxaliplatin, and encapsulating it in the fusion membrane. The nanodelivery system prepared by this invention exhibits pH-responsive drug release characteristics, generating H2S in the tumor microenvironment and H2 under light irradiation, while also possessing photocatalytic activity. This invention combines chemotherapy, photoelectrocatalytic therapy, and the regulation of multiple active substances, and can be used to prepare drugs for treating malignant tumors of the digestive system.

The invention relates to the technical field of physiological monitoring, in particular to a hepatocellular carcinoma treatment effect analysis system and method based on metabolism comprehensive analysis, and the method comprises the steps: obtaining the evolution condition of hepatocellular carcinoma, the composition condition of drugs and the composition condition of metabolites; drug absorption and transformation analysis is carried out based on the composition condition of the drug and the marking condition of the composition condition of the metabolite, future drug transformation component prediction is carried out based on the drug absorption and transformation analysis result and the evolution condition of the corresponding hepatocellular carcinoma, and drug treatment effect early warning is carried out based on the future drug transformation component prediction. The first-pass effect is corrected through mass spectrum imaging and enzyme activity, the inhibition effect of the tumor microenvironment on drug transformation is quantified, prediction is dynamically adjusted through the future tumor anomaly score ratio, and the accuracy of the time of drug replacement is improved.

The invention discloses a multifunctional double-drug delivery system based on metal collaborative treatment and application of the multifunctional double-drug delivery system, and belongs to the technical field of biological medicine. The double-drug delivery system is double-drug delivery lipidosome and comprises metal ions, a lipidosome membrane and active ingredients, the metal ions are adsorbed on the surface of the lipidosome membrane, and the active ingredients are wrapped in the lipidosome membrane; the metal ions are divalent metal ions; the active component consists of an STING agonist and a traditional Chinese medicine active monomer component. According to the double-drug delivery system, the STING agonist and the traditional Chinese medicine anti-inflammatory components are co-loaded through lipidosome, and multi-dimensional remodeling of a tumor microenvironment is achieved through the double effects of exciting tumor immunity and inhibiting inflammatory reaction; and meanwhile, by introducing metal ions, the lysosome escape efficiency of a liposome drug delivery system is effectively enhanced, so that the intracellular delivery efficiency of the drug is improved.

The invention relates to the technical field of biomedical detection, and discloses a system for detecting extracellular matrix free metalloproteinase and a soluble receptor. Comprising a polypeptide substrate nanopore sensing module used for detecting the enzyme activity of free metalloproteinase in an extracellular matrix; the electrophoretic analysis module is used for detecting a soluble receptor in an extracellular matrix, applying an electric field to a tumor microenvironment sample, determining the inter-terminal resistance of the sample by using an inter-terminal resistance detection device, and detecting the soluble receptor by comparing the resistance change according to the characteristic that the existence of the soluble receptor causes the additional resistance increase of the sample; and the data processing and judging module is electrically connected with the polypeptide substrate nanopore sensing module and the electrophoretic analysis module respectively, and is used for receiving the free metalloproteinase activity detection result and the soluble receptor detection result, and judging the time interval of cellular immune escape according to a preset rule in combination with cellular morphology observation information.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APCs.

The present invention relates to methods and conjugates to improve the penetrability of biological substances into the tumour microenvironment (TME) for therapeutic purposes, suitably the agent comprises at least: i a therapeutic domain; ii. a cleavable domain; and iii. a stabilisation domain.

The invention provides a lung cancer microenvironment ecological characteristic detection and curative effect evaluation system, and relates to the technical field of lung cancer prognosis evaluation, and the system comprises a reading module which is used for reading slice information of a subject; the boundary construction module is used for constructing a region boundary according to the tumor region in the slice information; identifying tumor infiltrating lymphocytes (TILs for short) from the slice information, and determining the distribution type of the tumor infiltrating lymphocytes in combination with the distribution characteristics and the region boundary of the tumor infiltrating lymphocytes; the method comprises the following steps of: obtaining slice information, identifying a three-level lymphatic structure (TLS for short) from the slice information, and determining a distribution type of the three-level lymphatic structure in combination with distribution characteristics and a region boundary of the three-level lymphatic structure; and the evaluation module is used for performing prognosis effect prediction on the subject based on the distribution type of tumor infiltration lymphocytes and the distribution type of the three-level lymphatic structure, deeply analyzing the immune condition of a tumor micro-environment (TME for short), and improving the accuracy of prognosis evaluation.

The present invention relates to the field of biomedicine, and in particular to immunogenic cell death-enhancing nanovesicle hydrogels and their applications. The present invention provides a 3D-printable, multifunctional, synergistic immunogenic cell death-enhancing nanovesicle hydrogel. The hydrogel uses SerMA hydrogel as a matrix and encapsulates cell membrane nanovesicles (N@ILO) loaded with the photothermal agent IR1061, the chemotherapy drug OXA, and the tumor acidic microenvironment regulator Lon. The hydrogel triggers initial tumor immunogenic cell death through the photothermal effect, further enhances the ICD effect through OXA, and modulates the acidic tumor microenvironment through Lon to increase T cell activity, achieving multimodal synergistic anti-tumor therapy after surgery. The hydrogel also possesses excellent photocurable 3D printing capabilities and can be used to construct personalized filling structures that match postoperative defect areas. The hydrogel has broad application prospects and provides a new strategy and theoretical basis for the comprehensive postoperative treatment of choroidal melanoma.

The application provides a tumor immune microenvironment multi-cell recognition and spatial analysis system, comprising: an intrinsic signal generation module generating an initial intrinsic signal vector; a preliminary functional marker module generating a preliminary phenotype classification label map based on spatial centroid coordinates of cell objects; a functional neighborhood construction module calculating and generating a functional neighborhood feature vector; a composite feature splicing module constructing a composite state feature vector; an effective function determination module decoding to obtain a continuous value feature vector output by a function determination model representing the final function strength under the regulation of the microenvironment; and a functional map rendering module rendering to generate a cell effective function map under the regulation of the environment. The application solves the problem that, in the prior art, when interpreting cell functions, the intrinsic state information of the cells and the local functional microenvironment context information cannot be effectively fused, resulting in deviation in the description of the spatial distribution map of tumor microenvironment function heterogeneity.

The embodiment of the invention provides a TPD52 immunomodulatory effect research method and system, and the method comprises the steps: obtaining single cell transcriptome data of a breast cancer tumor microenvironment; on the basis of the data, identifying the TPD52 as the immune regulation key dangerous gene by utilizing a machine learning algorithm; verifying the association of TPD52 expression and patient prognosis in a multi-center queue; and based on the function annotation and the body appearance type experiment of the TPD52, confirming the immunomodulatory effect of the TPD52, and outputting a comprehensive evaluation report of the immunomodulatory effect of the TPD52. According to the invention, a machine learning method and scRNA-seq are utilized to explore the effect of TPD52 as a key immunomodulatory factor in BRCA, and the application has important significance on tumor behavior and patient prognosis.

Disclosed is an application of a mechanical force sensitive macrophage subset in pancreatic cancer diagnosis or prognosis evaluation, in which it is found that a number of mechanical force sensitive macrophages of CD68+p-PYK2+YAP1+ in pancreatic cancer is obviously higher than that of an adjacent normal tissue, and the number of the macrophages is in positive correlation with a pancreatic cancer process, so that the mechanical force sensitive macrophages can be used as a pancreatic cancer diagnosis and prognosis index. An elasticity modulus of the cells is reduced by inhibiting a mechanical force check point PYK2 of monocytes / macrophages, and differentiation of the monocytes into the macrophages is inhibited, so that a tumor micro-environment of the pancreatic cancer is improved. Growth of the pancreatic cancer is remarkably inhibited through combined treatment, and the lifetime of mice with the pancreatic cancer is remarkably prolonged.

The present invention describes novel drug-carrying nanoparticles called bionanocarriers capable of modulating the cellular redox system and targeting the cancerous tumor.Specifically, the invention relates to a nanomedicine strategy for combating cancerous tumor cells, a strategy that aims to target the tumor, and consists of providing quercetin-linked magnetite nanoparticles (Q): (MNPs Q), and 3,5-dimaleylbenzoic acid-linked magnetite nanoparticles (A3'5DMB): (MNPs A3'5DMB)M; both types of nanoparticles were subsequently encapsulated with chitosan (Qs) and O-carboxymethyl chitosan (O-CMQs), functionalized with 11-mercaptoundecanoic acid (MUDA), and finally the anti-ABCC3 antibody was attached to the polymer phase, which was used as a selective driver of the delivery process of the encapsulated nanoparticles, thus carrying out the construction of the bionanocarriers: BNC-1: MNPs-Q-Ab; BNC-2: MNPs-a3'5DMB-Ab.Its manufacturing method and the tests of its biological functionality, its stability, the degradation of the encapsulation for the tumor microenvironment, the controlled release profile of the drugs Q and A3'5DMB, selective cell uptake, intracellular localization, cytotoxic effect on steroids of hepatocellular carcinoma cells with altered redox balance and induction of apoptosis, as well as its safety on normal cells, are described.

There is provided a gastric tissue tumour model that is three-dimensional comprising from 0.8 to 1.2 w / v % alginate, from 1.7 to 2.3 w / v % gelatin and gastric decellularized extracellular matrix (dECM). The gastric tissue model is for example an esophageal cancer tumour model which advantageously replicates the tumour microenvironment for esophageal cancer and can be used to perform a three-dimensional culture of esophageal tumour cells or metastatic cells that often metastasize into the esophagus.

The invention provides application of a GPX1 inhibitor combined with a copper death inducer in preparation of a cold tumor treatment medicine. The key node effect of GPX1 in cold tumor metabolism reprogramming is found and utilized. In a cold tumor microenvironment deficient in glutamine, tumor cells often resist a copper death inducer. Through targeted inhibition of GPX1, the sensitivity of cold tumor cells to copper ion toxicity is significantly enhanced, and the drug resistance problem caused by metabolic pressure is effectively overcome.

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.

There is provided the combination of Bacillus Calmette-Guérin (BCG) vaccine and β-glucan adjuvant for the treatment of a cancer characterized by the presence of protumoral T3 neutrophils in the tumour microenvironment. The β-glucan is characterized by a μ-1,3 glucose backbone. The BCG and β-glucan combination demonstrated a synergistic effect in remodeling the tumour microenvironment to resist conversion of neutrophils into the T3 phenotype. The cancer can be bladder cancer, melanoma, lung adenocarcinoma, head and neck squamous cell cancer, pancreatic adenocarcinoma, low-grade gliomas, esophageal carcinoma, and cervical squamous cell carcinoma.

The invention discloses a hypoxia activating peptide-photosensitizer-drug conjugate and a preparation method and application thereof in the technical field of medicine, the conjugate takes indocyanine with a high molar extinction coefficient as a photosensitive core, distorted conjugate units are introduced to two sides of indole, the characteristic of'limited movement in molecules' is given to the conjugate, and radiation and non-radiation energy dissipation are balanced. Meanwhile, an azo bond sensitive to hypoxia is reasonably introduced between a light treatment module and a chemotherapy module to serve as a responsive linker, and is further coupled with two-molecule integrin targeting peptide cRGD, so that the azo bond is self-assembled into nanospheres in an aqueous solution, and a triple targeting mechanism, namely multivalent integrin receptor targeting, aggregation and tumor microenvironment hypoxia selective activation, is realized. In an in-situ osteosarcoma mouse model, the conjugate realizes real-time near-infrared two-region imaging, shows potent tumor inhibition, effectively inhibits lung metastasis, and does not detect obvious systemic toxicity.

The invention discloses an inhibitor-loaded oncolytic microgel as well as a preparation method and application thereof, and the inhibitor-loaded oncolytic microgel is an oncolytic microgel (OMG) with similar activity and immune activation capability to an oncolytic peptide, and can efficiently entrap an immune checkpoint inhibitor and realize adjustable drug sustained release so as to enhance the cancer immunotherapy effect. The oncolytic microgel can effectively maintain the biological activity of entrapped drugs and antibodies, and has wide application prospects in the fields of drug controlled release and the like. Meanwhile, single injection of OMG (P1C4-OMG) loaded with anti-PD-1 and anti-CTLA-4 in a tumor can effectively reverse an inhibitory tumor microenvironment, enhance anti-tumor immune response and realize a remarkable tumor inhibition effect and outstanding survival benefits, and the oncolytic microgel with the adjustable antibody release function is a safe and unique cancer immunotherapy platform.

The invention relates to the technical field of medical instruments, in particular to a microwave ablation instrument and a preparation method thereof. The microwave ablation instrument provided by the invention comprises a microwave needle body, a sodium alginate-calcium ion cross-linked network loaded on the surface of the microwave needle body and drug-loaded calcium carbonate adsorbed by the sodium alginate-calcium ion cross-linked network, the drug-loaded calcium carbonate comprises mesoporous CaCO3 and a demethylation drug loaded in the mesoporous CaCO3 and / or on the surface of the mesoporous CaCO3. The microwave ablation apparatus provided by the invention can reduce the risk of needle passage metastasis, significantly improve the local drug concentration of the tumor, respond to the tumor microenvironment, and improve the tumor treatment effect. Through targeted delivery, multi-mechanism cooperation and immune microenvironment regulation and control, a multi-dimensional treatment breakthrough from local ablation to system immune activation is realized, and the preparation is remarkably superior to the prior art in the aspects of curative effect accuracy, safety and long-acting recurrence / metastasis resistance.

The invention provides a near-infrared NIR-II region fluorescence ratio probe based on tumor-associated neutrophil and application of the near-infrared NIR-II region fluorescence ratio probe. The nanoprobe is a rare earth doped down-conversion nanocrystal with a core-shell structure, the surface of the rare earth doped down-conversion nanocrystal is modified with a response unit and a targeting unit, and the response unit can release a fluorescence signal through enzymatic cleavage of neutrophil elastase; and the targeting unit is used for targeting a tumor microenvironment integrin receptor. The nanoprobe has high specificity and sensitivity, high anti-interference capability and self-calibration capability, can realize NIR-IIb region ratio imaging, provides a key basis for early curative effect judgment, achieves accurate individual stratification, fills the technical blank of cancer immunotherapy curative effect monitoring, and promotes the development of a tumor immune microenvironment molecular imaging technology.

The application discloses a kind of liposome nanoparticles for encapsulating lysine and regulated tumor organoid model.The liposome nanoparticles are prepared by thin film hydration method with DSPC,cholesterol and mPEG-DSPE as membrane material,encapsulate lysine in internal water phase,particle size is 70-250 nm,PDI is less than 0.2,encapsulation efficiency is 8%-20%,drug loading rate is 2%-50%.Tumor organoids can effectively uptake the nanoparticles,and release lysine in response to acidic microenvironment,neutralize intracellular and microenvironment acidity,adjust pH to 7.2-7.4.Based on the liposome constructed tumor organoid model,neutral pH environment can be maintained in vitro for a long time,which is used to evaluate the true efficacy of weakly alkaline chemotherapeutic drugs and overcome the problem of underestimation of efficacy caused by traditional acidic model.The application provides a method for regulating tumor microenvironment and a new evaluation tool for pH-responsive drug screening.

The present invention belongs to the field of biomedicine technology, and specifically relates to a near-infrared II fluorine-doped carbon dot nanozyme (F‑CDs@PEG) for photothermal-enhanced catalytic immunotherapy, as well as its preparation method and application. F‑CDs excel in NIR-II fluorescence emission for in vivo bioimaging and NIR photothermal therapy, and also possess photothermally enhanced Gox-like, POD-like, and GSH-px activities, which can be used to disrupt the energy metabolism and redox balance of tumor cells, enhance immunotherapy, and reshape the tumor microenvironment. Photothermal-enhanced immunotherapy induces tumor immunogenic cell death and further promotes the maturation of antigen-presenting cells such as DCs, thereby enhancing T cell infiltration within the tumor. In addition, F‑CDs@PEG reduces G‑CSF levels under NIR (808nm) laser irradiation, thereby inhibiting MDSC levels, alleviating T cell exhaustion, and effectively inhibiting tumor growth; the photothermal-enhanced catalytic immunotherapy mediated by F‑CDs@PEG can induce strong immune memory and have a long-term inhibitory effect on recurrent tumors.

The invention discloses an application of a macrophage subgroup in improving the treatment effect of AK112 (Adenosine Kinase 112). The macrophage subgroup is APOE + KRT18-CCL20-macrophages. It is found for the first time that a specific macrophage subset in a tumor microenvironment (TME) can significantly improve the AK112 double-antibody tumor killing activity, and a new target is provided for overcoming clinical drug resistance. Meanwhile, a matched flow cytometry kit is developed, the kit comprises 12 antibody combinations, and the subgroup marker is synchronously and accurately detected by a single tube through a full-spectrum flow technology. The sensitivity and the specificity are high, the AK112 treatment response can be dynamically monitored, and the disease progress can be predicted. According to the macrophage targeted synergistic mechanism and the integrated detection system, a combined treatment strategy is provided for AK112 drug-resistant patients, and a pioneering tool is provided for individualized curative effect evaluation.

The invention relates to the technical field of targeted drug-loaded nanobubbles, and discloses a targeted drug-loaded nanobubble and a preparation method and application thereof, and the targeted drug-loaded nanobubble is prepared by chemically connecting GEM and cholesterol through an amide reaction. According to the scheme, the characteristic that a cholesterol shell of the nano-bubble can be combined with NPC1L1 with ultrahigh expression of pancreatic cancer cells in a targeting manner is utilized, and a chemotherapeutic drug GEM is carried on the shell of the nano-bubble, so that the targeting GEM-loaded nano-bubble is constructed. The ultrasonic molecular imaging characteristics of the nano-bubble after penetrating through tumor blood vessels and being combined with pancreatic cancer cells in a targeted manner and the effect of the nano-bubble on relieving CD8 + T cell immunosuppression in a tumor microenvironment are researched and discussed, and the effect of ultrasonic irradiation nano-bubble burst to release GEM to accurately kill pancreatic cancer cells and improve the synergistic treatment effect of the tumor immune microenvironment is clarified; a safe and effective brand-new strategy for synergistic chemotherapy and immune combined treatment is provided for diagnosis and treatment of pancreatic cancer.