912 results about "Tumor Microenvironments" patented technology

The invention discloses an intestinal cancer immune response graph neural network prediction method, a medium and equipment, and the method comprises the steps: collecting pathological image information, immunodetection information and basic clinical information, extracting a tissue space distribution characteristic spectrum through a deep convolutional network, and constructing a graph neural network model in combination with an immunomarker expression characteristic matrix; spatial interaction characteristics of a tumor microenvironment are modeled by adopting a graph attention mechanism, finally a treatment response probability, an optimal treatment opportunity and an adverse reaction risk are predicted through a multi-task learning framework, and a clinical decision report containing a prediction response curve, a risk early warning threshold and a treatment time window suggestion is output. According to the method, through multi-modal data fusion and spatial interaction modeling, accurate prediction of intestinal cancer immunotherapy response is realized, and a more comprehensive reference basis is provided for clinical decision making.

The invention discloses a colorectal cancer drug relocation method based on multi-omics integration. The system comprises a multi-omics data acquisition and preprocessing module, a tumor microenvironment analysis module, a specific disease network construction module, a multi-dimensional drug relocation module and a result evaluation module. And the tumor microenvironment analysis module comprises cell heterogeneity identification, cell map construction, cell annotation and tumor cell subset annotation. The specific disease network construction module comprises tumor feature expression program extraction, expression program screening, meta-program construction, clinical related meta-program recognition and specific disease protein interaction network construction. And the multi-dimensional drug relocation module comprises a module for identifying diseases by using a random walk algorithm, carrying out drug screening based on disturbance data, carrying out drug screening based on network proximity and carrying out comprehensive drug relocation. From the perspective of single cell data, element programs related to colorectal cancer survival are excavated, corresponding modules are designed, and the efficiency and precision of colorectal cancer targeted drug screening are improved.

The invention discloses an OTX-015 (Ox-015) loaded cascaded responsive nano particle and a preparation method thereof. The nanoparticle has a three-layer core-shell structure, wherein the innermost layer is a cross-linked nanoparticle of chitosan and paclitaxel; the middle layer is a polydopamine layer loaded with a bromodomain inhibitor OTX-015; the outermost layer is a gelatin layer grafted with babali; wherein the cross-linked substance of the chitosan and the paclitaxel is a cross-linked substance containing a disulfide bond. The invention also provides a preparation method of the cascade responsive nano-particle and application of the cascade responsive nano-particle in preparation of an antitumor drug targeted delivery system. The nanoparticle provided by the invention improves the tumor microenvironment while activating in-vivo autoimmunity, and kills tumor cells by using photothermal therapy assisted chemotherapy drugs, so that the synergistic effect of chemotherapy / photothermal therapy / immunotherapy is realized, and a new idea is provided for clinical tumor treatment.

The invention belongs to the technical field of engineered probiotics, and particularly relates to engineered probiotics for radiosensitization and tumor metabolism regulation as well as a preparation method and application of the engineered probiotics. The engineering probiotics comprise probiotics and core-shell type metal nanoparticles which are loaded on the probiotics and are synthesized through a biological directional mineralization effect; the core of the core-shell type metal nanoparticle is a palladium element, and the outer layer of the core-shell type metal nanoparticle is a palladium element and a gold element. The engineering probiotics provided by the invention have excellent enzyme catalysis performance and can target and retain in tumor sites, and through the synergistic effect of all components in the engineering probiotics, adenosine metabolism is effectively inhibited, secretion of pro-inflammatory cytokines is enhanced, tumor microenvironment is promoted to be converted into an inflammatory state, up-regulation of immune checkpoints is inhibited, and the immune checkpoints are inhibited. And T cells are inhibited from being transformed into depletion phenotype and transformed into effect type from depletion type. After the SBRT and the immune checkpoint inhibitor are combined for use, the growth of tumors can be effectively inhibited, and the effect of enhancing immune radiotherapy is achieved.

The invention discloses a hepatocellular carcinoma postoperative early recurrence prediction method based on multi-modal fusion. The method comprises the following steps: firstly, integrating clinical data of a training set, a preoperative enhanced CT image and a postoperative full-view digital pathological image, and carrying out standardized correction; then, traditional image omics features and deep learning features are extracted from the CT image, cell nucleus morphological features and tumor microenvironment spatial configuration features are extracted from the pathological image, and key feature signatures are screened out through a maximum correlation minimum redundancy algorithm (mRMR) and LASSO regression in combination with clinical features. And then carrying out progressive model construction by adopting an XGBoost algorithm, sequentially establishing a clinical single-mode model, an image single-mode model, a pathological single-mode model and a multi-mode fusion model, and explaining and visualizing the models by utilizing an SHAP value and a Grad-CAM technology. Finally, the performance of the model is evaluated in a multi-dimensional mode through internal cross validation, foresight and external independent validation, risk layering is carried out based on the prediction probability, and individualized postoperative management is guided.

The invention provides a nano-drug based on atomic layer deposition and a preparation method of the nano-drug, mesoporous silica is taken as a carrier, bimetallic nanoparticles are precisely deposited through ALD, and chemotherapeutic drugs and antibacterial components are loaded by combining amination and targeted PEG modification, so that the following functions are realized: (1) H2O2 in a tumor microenvironment is catalyzed to generate reactive oxygen species (ROS); removing fusobacterium nucleatum and damaging a biological membrane of the fusobacterium nucleatum; (2) GSH is consumed through Fenton reaction, and tumor drug resistance is reversed; and (3) the drug is released in pH response, and tumor cells are accurately killed. The invention further provides application of the nano-drug based on atomic layer deposition in treatment of related drug-resistant colorectal cancer induced by fusobacterium nucleatum, the process is controllable, the biocompatibility is excellent, the treatment effect on the drug-resistant colorectal cancer is remarkably improved, and the nano-drug has wide clinical application prospects.

The invention provides a micro-fluidic chip, a model for realizing accurate positioning of an organoid and sequential interaction of a tumor microenvironment, and a construction method of the model. The micro-fluidic chip comprises a chip main body and a chip bottom plate, a blood vessel channel, a central channel, a neural immune cell channel and a culture medium channel are sequentially arranged on the lower surface of the chip main body; the chip bottom plate is arranged on the lower surface of the chip main body and seals each channel; one side of the blood vessel channel is communicated with one side of the central channel, the other side of the central channel is communicated with one side of the neural immune cell channel, and the other side of the neural immune cell channel is communicated with one side of the culture medium channel; the upper surface of the chip main body is provided with an open hole, and the open hole penetrates through the chip main body and is communicated with the middle position of the central channel. According to the model manufactured by the micro-fluidic chip, accurate positioning of tumor organs can be realized through combination of an automatic positioning device and physical constraint, and multi-dimensional cell interaction is supported by dynamic environment regulation and control.

The invention relates to a double-framework self-developing embolism system based on iodine modified PNIPAM gel and cross-linked albumin microspheres, which simulates a brick wall-concrete effect through a microsphere-gel composite structure and synergistically improves the embolism strength. A novel TACE treatment system is designed and constructed, multiple effects of tracing, embolism, hypoxia enhanced chemotherapy and tumor microenvironment improvement are achieved through the self-developing temperature-sensitive gel-drug carrying microspheres, and the anti-tumor effect is cooperatively improved.

The invention relates to the technical field of antitumor drugs, in particular to a Ru (II) complex and a preparation method and application thereof, and the Ru (II) complex has a structure as shown in a formula I. The Ru (II) complex synthesized by the method disclosed by the invention not only has relatively high cytotoxicity, but also has good photodynamic antitumor activity. After the complex is illuminated, the efficiency of the complex entering cells in an active transportation mode can be accelerated, mitochondria and endoplasmic reticulum are targeted at the same time, mitochondrial membrane potential decline and endoplasmic reticulum stress are caused to form a dual organelle damage effect, immunogenic cell death is caused, the tumor microenvironment is adjusted, and the tumor cell immunogenicity is improved. The enrichment of dendritic cells (DCs) in tumor cells is realized, the chemotactic activity of effector T cells is improved, the proportion of CD4 < + > and Foxp3 < + > cell populations is reduced, and finally the anti-tumor immune response is activated. Meanwhile, the complex provided by the invention can also induce the cell to generate pan apoptosis, retard the cell cycle in the G2 / M period and enhance the effect of the complex in inhibiting tumor proliferation.

The invention discloses a spatial transcriptome data analysis method based on artificial intelligence, and belongs to the technical field of spatial transcriptomics data analysis. Firstly, self-adaptive normalization and hypervariant gene screening preprocessing are carried out on original gene expression data; then constructing a hierarchical map integrating spatial proximity and transcription similarity, and ensuring the connectivity and robustness of the map through a dynamic radius pruning and neighborhood inheritance strategy; dividing positive and negative sample sets based on the atlas, and inputting a type modulation contrast graph auto-encoder for training; and finally, spatial domain identification and downstream function analysis are completed based on the low-dimensional potential representation or reconstructed gene expression matrix output by the model. The method effectively improves the accuracy and stability of spatial domain recognition, adapts to multi-technology-source data, enhances the biological interpretability of model output, and can be widely applied to biomedical scenes such as tumor microenvironment analysis and organ development research.

The invention relates to the field of biology, and provides a human immortalized pancreatic cancer fibroblast as well as a preparation method and application thereof.The human immortalized pancreatic cancer fibroblast comprises three cell strains which are all primary fibroblast cells extracted from tumor tissues of pancreatic ductal adenocarcinoma patients, the human pancreatic cancer fibroblast cell strain CAFPC-2209131, the human pancreatic cancer fibroblast cell strain CAFPC-2209132 and the human pancreatic cancer fibroblast cell strain CAFPC-2303221 are classified and named as the human pancreatic cancer fibroblast cell strain CAFPC-2209131, the human pancreatic cancer fibroblast cell strain CAFPC-2209132 and the human pancreatic cancer fibroblast cell strain CAFPC-2303221 respectively, the human pancreatic cancer fibroblast cell strain CAFPC-2209132 and the human pancreatic cancer fibroblast cell strain CAFPC-2303221 are all Cell STR identification and immunofluorescence detection prove that the cell strain is a fibroblast cell strain. After the tumor-associated fibroblast and pancreatic cancer cells are co-cultured, the proliferation ability of the tumor cells is obviously enhanced, and the sensitivity of the tumor cells to a chemotherapeutic drug gemcitabine is reduced. A new thought is provided for diagnosis and treatment of pancreatic cancer, and based on the pancreatic cancer in-vitro co-culture model established in vitro, the application has important significance for researching the effect and related mechanisms of fibroblasts in the pancreatic cancer tumor microenvironment.

The invention belongs to the field of biomedicine, and particularly relates to application of Ikbkb inhibited or knocked-out macrophages in preparation of breast cancer radiotherapy sensitizing drugs. The inventor of the invention proves the effect of the macrophage of which the Ikbkb is inhibited or knocked out in breast cancer radiotherapy for the first time. Compared with the strategy of mainly depending on small molecule drugs or antibodies in the prior art, the tumor growth can be more effectively inhibited after the macrophages in the tumor microenvironment are transformed and the Ikbkb knockout engineered macrophages are subjected to combined radiotherapy, and a brand new solution is provided for overcoming breast cancer radiotherapy resistance.

The invention discloses a drug delivery system based on branched chain nucleic acid as well as a preparation method and application of the drug delivery system. The drug delivery system comprises a multivalent nucleic acid framework, a nucleic acid-small molecule coupling drug and a nucleic acid-polypeptide coupling drug, a nucleic acid nanostructure is formed through base complementary pairing assembly, and the nucleic acid-small molecule coupling drug comprises first nucleic acid and an E3 ubiquitin ligase ligand coupled with the first nucleic acid; the nucleic acid-polypeptide coupling drug comprises a second nucleic acid and a cell penetrating peptide coupled with the second nucleic acid. The drug delivery system disclosed by the invention can respond to a tumor microenvironment, so that cell penetrating peptides are activated, tumor penetrating and cytoplasm delivery capacities are enhanced, the aim of efficiently degrading tumor-related target proteins is fulfilled by combining a multivalent effect, and a remarkable tumor treatment effect is achieved; in addition, the preparation method is simple and easy to implement, has universality and high production efficiency, and is expected to be applied to treatment of various tumors.

The invention relates to the technical field of vaccines, and discloses a preparation method and application of an anti-tumor vaccine based on an autoantigen and a synthetic antigen. The anti-tumor vaccine comprises a tumor autoantigen and a synthetic antigen, wherein the tumor autoantigen is extracted from a tumor cell membrane, a tumor cell lysate, a tumor cell secretion, an exosome antigen or an antigen released by a tumor microenvironment; the synthetic antigen is selected from at least one of a tumor associated antigen, a tumor specific antigen, a personalized neoantigen, a pathogen antigen, a biotoxin, a biomolecule antigen and coding nucleic acid of a peptide type antigen in the antigens; the coding nucleic acid is DNA or mRNA. The vaccine molecule composed of the tumor autoantigen and the synthetic antigen is easy to prepare, has a strong anti-tumor immune effect and good biological safety, solves the problems that the traditional tumor autoantigen has no specific precise target spot and the synthetic antigen is single in immunogen, and has a wide application prospect.

The invention relates to the technical field of photo-thermal gas treatment, in particular to a pH response type conjugated polymer nano-composite particle as well as a preparation method and application thereof, and develops a conjugated polymer nano-composite particle IN-20-(NH4) 2S capable of intelligently responding to acidic pH in a tumor microenvironment, which is used for photo-thermal and gas synergistic treatment of tumors. The nanoparticles generate heat under NIR-II light induction to promote the conjugated polymer composite material to release (NH4) 2S, the (NH4) 2S responds to acidic pH and can react with acid to generate H2S, the concentration of the (NH4) 2S is gradually increased along with time, the release amount of the (NH4) 2S is more remarkable under the illumination condition, and a new strategy is provided for enhancing the accuracy and effectiveness of tumor treatment.

The invention relates to an STING gene knockout TIL capable of enhancing anti-tumor activity and a preparation method and application of the TIL, in particular to a genetically engineered immune cell, and an STING gene in the genetically engineered immune cell is silenced or down-regulated. The ferroptosis resistance of the immune cell provided by the invention is remarkably enhanced, the immune cell can be better infiltrated into a tumor microenvironment, and the immune cell has a remarkable anti-tumor effect.

The invention relates to the technical field of medicines, in particular to a composite nano vaccine and application thereof. The composite nano vaccine is prepared by coupling a natural compound with endoplasmic reticulum stress induction capability on the surface of Ga-MOF nano particles. The composite nano vaccine can significantly enhance the anti-tumor effect through a ferroptosis mechanism, an endoplasmic reticulum stress and immunogenic cell death mechanism and a cryoablation technology synergistic effect mechanism, reverses an immunosuppressed tumor microenvironment, inhibits the growth of primary tumors and distant metastatic tumors, and has a good anti-tumor effect. A brand new strategy is provided for comprehensive treatment of tumors, and the application prospect is wide.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

The invention relates to the field of drug discovery and delivery collaboration, in particular to an autonomous evolutionary drug discovery and delivery collaboration method and system based on a large language model. The method comprises the following steps: aiming at a given biological target three-dimensional structure, generating a candidate molecular library which is complementary with a target pocket and gives consideration to druggability through an SE (3) isovariant hybrid generation model; according to a two-stage funnel type high-throughput virtual screening process, screening out the molecule with the highest comprehensive potential from the candidate molecule library; generating a customized delivery scheme through a three-stage process; in a digital twinborn model for simulating a real in-vivo tumor microenvironment, a targeted delivery process of a drug and carrier complex is simulated, and efficiency is evaluated; atomic-scale performance confirmation is carried out on a medicine, carrier and target point ternary system through molecular dynamics simulation. The invention is suitable for drug research and development.

The invention discloses iron oxide nanoparticles capable of responding to particle size change in a tumor microenvironment and a preparation method of the iron oxide nanoparticles, and belongs to the technical field of biomedical nano materials. The nano-particle comprises an iron oxide nano-crystal core with the particle size of 3-5nm and a tumor microenvironment response layer coating the surface of the iron oxide nano-crystal core. The response layer contains groups, such as disulfide bonds, enzyme digestion peptide fragments and the like, which can respond to acidic pH, high-concentration reduced glutathione or matrix metalloproteinase and other tumor characteristic stimuli to generate structural changes. In a tumor microenvironment, the hydration particle size of the nanoparticles can be directionally and controllably converted from 3-20 nm to 20-100 nm (or reversely). The preparation method mainly comprises two steps of preparing the core by a thermal decomposition method and modifying the surface response layer. The technical problems of insufficient tumor targeted enrichment capacity, limited imaging contrast and difficulty in balancing permeation and retention caused by fixed particle size of the existing iron oxide nanoparticles are solved, and the accuracy and efficiency of tumor diagnosis and treatment can be remarkably improved.

The invention discloses a modular tumor microenvironment response polypeptide and a preparation method and application thereof. The modular tumor microenvironment response polypeptide is composed of the following functional modules: a targeting and chemotactic module used for targeting tumor cell surface p32 protein and tumor lymphatic vessels and promoting tumor tissue penetration and enrichment; the microenvironment double-response module is used for being cut by MMP-2 / 9 enzyme and broken by high-concentration glutathione GSH in a tumor microenvironment to trigger self-assembly; the self-assembly driving module is used for exposing after the microenvironment responds to activation and driving short peptides to be self-assembled to form a nano structure; a killing module: a pro-apoptotic peptide PAD used for targeting a mitochondrial membrane and inducing tumor cell apoptosis; and the stability optimization module is used for enhancing the degradation resistance of the oligopeptide. By integrating targeted delivery, enzyme digestion response, acid-sensitive release and stabilizing structures, the problems of insufficient targeting property, inaccurate release, poor stability, diagnosis-treatment splitting and the like of the anti-tumor drug and the developing agent are solved.

The invention provides a multi-view space transcriptomics clustering method based on sharing-specific information mining. The technical problems that in an existing space domain recognition method, robustness of a single view is insufficient, multi-view information fusion is insufficient, and description of data statistical characteristics is not accurate are solved. According to the technical scheme, the method comprises the following steps: S1, acquiring and preprocessing original data of a spatial transcriptome; s2, constructing a sharing-specific decomposition coding network; s3, using a ZINB expression decoder, a structure decoder and a Student's t distribution clustering module to construct a multi-task loss function; and S4, outputting a spatial domain division result based on the trained network. According to the method, the spatial domain recognition precision and robustness are remarkably superior to those of an existing method, the data statistical characteristics and biological significance can be accurately described, stable support is provided for tissue function analysis and tumor microenvironment research, and the analysis quality and application value of spatial transcriptomics data are effectively improved.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

The invention discloses a cell lineage tracking system based on synNotch and CRISPR / Cas9 bar code technology and application thereof, the cell lineage tracking system comprises a system mGFP ligand vector for constructing Sender ligand cells and a system for constructing Receiver recipient cells, and the system comprises a synNotch receptor-rtTA fusion vector, a TetO-Cas9 expression vector, a gRNA expression vector and a Target vector library containing a Barcode sequence. A synNotch system and a CRISPR / Cas9 gene editing technology are combined with a bar code strategy, a unique bar code is generated, the contact sequence between cells is recorded, the method is compatible with a single-cell sequencing technology, transcription information of the cells is provided, long-term tracking of the contact history between the cells is achieved, the method can be used for tracking interaction and functions between the cells in a tumor microenvironment, and the application prospect is wide. Through long-term tracking and functional analysis of interaction between macrophages, especially macrophages and tumor cells, the accuracy of interaction analysis is remarkably improved, and a more accurate target spot is provided for targeted therapy.

The invention belongs to the technical field of biological medicine, and particularly discloses nano composite particles based on a metal organic framework and a preparation method and application of the nano composite particles. The nano-composite particles are constructed through electron adsorption and coordination based on a nano-scale metal organic framework, and under the acidic microenvironment and ultrasonic irradiation of tumors, the nano-composite particles can be decomposed and released in a responsive manner, play a role of a sound-sensitive agent, generate a large amount of active oxygen and induce tumor cells to generate immunogenic death, so that the tumor cell immunogenicity is improved, and the tumor cell immunogenicity is improved. Further, more cytotoxic T lymphocytes are promoted to infiltrate a tumor microenvironment, T cell mediated anti-tumor immune response is recovered, and tumor metastasis is effectively prevented. The carrier metal organic framework ZIF8 of the nano-composite particles can serve as a sound-sensitive agent to generate active oxygen, the function of ultrasonic imaging of tumor tissue can be achieved, the effect of diagnosis is achieved while treatment is conducted, tumor diagnosis and treatment monitoring can be achieved at the same time through one-time drug administration, and a new strategy is provided for precise medical treatment.

The present invention provides variant forms of anti-CTLA-4 antibodies, such as ipilimumab, that preferentially bind to CTLA-4 at low pH. Such antibody variants exhibit preferential activity in the tumor microenvironment, an enhanced ratio of anti-tumor response to side-effects, and an enhanced therapeutic index.

The invention relates to the technical field of biological medicine nano-drug delivery, in particular to a nano-drug delivery system based on a metal polyphenol network, and solves the problems that an existing MPN nano-drug delivery system is low in drug loading capacity, obvious in burst release, poor in stability, single in response and lack of targeting capacity. The system comprises a nanoparticle core formed by self-assembly of metal ions and polyphenol compounds, the surface of the nanoparticle core is coated with a biocompatible polymer shell, a hydrophobic drug is loaded inside the nanoparticle core, the particle size of the nanoparticle core is 50-300 nanometers, the nanoparticle core has pH responsiveness and a dynamic reversible coordination structure, and an organic solvent is not needed in the preparation process. The drug loading efficiency is remarkably improved, burst release is inhibited, the in-vivo stability is enhanced, tumor microenvironment responsive drug release is achieved, the circulation time is prolonged through the polymer shell, tumor accumulation is improved, and a safe and controllable delivery platform is provided for precise and efficient treatment.

Provided herein are activatable anti-human CTLA-4 antibodies comprising a heavy chain comprising a VH domain and a light chain comprising a masking moiety (MM), a cleavable moiety (CM), and a VL domain. Such activatable anti-human CTLA-4 antibodies have CTLA-4 binding activity in the tumor microenvironment, where the masking moiety is removed by proteolytic cleavage of the cleavable moiety by tumor-specific proteases, but exhibit greatly reduced binding to CTLA-4 outside the tumor. In this way, the activatable anti-human CTLA-4 antibodies of the present invention retain anti-tumor activity while reducing the side effects associated with anti-CTLA-4 activity outside the tumor.

The invention discloses an aptamer-modified lipid nano delivery platform as well as a preparation method and application thereof, and belongs to the field of biomedicine. The platform is prepared by taking DPPC, DOTAP and cholesterol as basic lipid components, Ce6 as a sound-sensitive agent and Flt3L as an immune agonist, controlling the particle size through gradient extrusion, and coupling cholesterol with an EpCAM aptamer for surface modification. The method has the core advantages that active targeting enrichment of tumors is realized by virtue of the aptamer, tumor cell immunogen cell death (ICD) is induced in combination with a sonodynamic therapy (SDT), and damage-related molecular patterns (DAMPs) are released; meanwhile, Flt3L is released in a tumor microenvironment, collection and activation of type 1 classical dendritic cells (cDC1) are specifically promoted, an'endogenous cDC1 vaccine 'is constructed, and CD8 + T cell mediated anti-tumor immune response is enhanced. Experiments prove that the platform can significantly improve the cDC1 infiltration level of a tumor site, effectively inhibit the progress of prostate cancer (PCa), and provide a new normal form for immune'cold tumor 'treatment.

The invention relates to the field and discloses application of terahertz waves or intermediate infrared in preparation of adoptive T lymphocytes. The Terahertz wave or mid-infrared modulation technology is utilized to specifically regulate and control the functions of the T cells in a flowing irradiation mode, and the functions of the T cells from different sources are enhanced under the conditions that no medicine is used and no exogenous gene is introduced. Terahertz wave or mid-infrared stimulation is applied to the T cells in a flowing irradiation mode, specific terahertz wave or mid-infrared frequency for remarkably enhancing the functions of the T cells is determined in a frequency screening mode, and after the optimal irradiation frequency is determined, the T cells with the most remarkable function improvement are further input back into a donor. The T cells stimulated by terahertz waves or mid-infrared rays can play a powerful immune function in a tumor microenvironment so as to inhibit further development of tumors.