154 results about "Tumor Microenvironments" patented technology

This invention relates to a method and application for enriching circulating tumor cells (CTCs) based on ambient temperature mechanical perfusion technology, belonging to the field of biomedical technology. The method comprises the following steps: flushing the liver resected during liver transplantation via the portal vein and hepatic artery, connecting it to an ambient temperature mechanical perfusion loop, and performing in vitro perfusion using simulated blood perfusion fluid; when perfusion exceeds 2 hours and the lactate content drops to <5 mmol / L, collecting the simulated blood perfusion fluid; and sequentially subjecting the simulated blood perfusion fluid to centrifugation, red blood cell removal, and white blood cell removal to obtain enriched circulating tumor cells (CTCs) for liver cancer. A human liver cancer ex vivo organ perfusion model is constructed using NMP technology to fully recreate the tumor microenvironment and CTC generation process, and the large volume of perfusion fluid is processed to achieve efficient enrichment of CTCs.

This invention discloses a method for preparing a core-shell microneedle patch loaded with dual nanoparticles, comprising: preparing silica nanoparticles loaded with oxyhemoglobin and dihydroporphyrin e6; preparing calcium carbonate nanoparticles loaded with aPD-1 antibody; dispersing the silica nanoparticles loaded with oxyhemoglobin and dihydroporphyrin e6 in a polyvinyl alcohol solution to prepare the shell structure of the microneedles; preparing a polymer hydrogel; dispersing the calcium carbonate nanoparticles loaded with aPD-1 antibody in the polymer hydrogel to prepare the core structure of the microneedles; and casting the polyvinyl alcohol solution onto the backing of the microneedles to finally obtain the core-shell microneedle patch loaded with dual nanoparticles. The core-shell microneedle patch loaded with dual nanoparticles prepared by this invention can deliver nanoparticles to the tumor site, where the nanoparticles respond to the tumor microenvironment and activate the body's own immune system, thereby achieving a therapeutic effect on tumors.

This application discloses a method, system, and device for analyzing the state of the tumor microenvironment based on medical images, relating to the field of medical image processing technology. First, by acquiring medical images and gene expression data of related tissues within those images, the medical images are preprocessed to obtain image patches, and semantic features of these patches are extracted. An algorithm is then used to calculate a predefined immune resistance mechanism that matches the gene expression data as the dominant immune resistance mechanism. This dominant immune resistance mechanism is then set as a supervisory label for the model, and a prediction model is constructed. The model is trained using a large amount of data, and the medical image to be analyzed is input into the trained prediction model to obtain the predicted category of the resistance mechanism. This application can accurately predict the resistance mechanism of pathological tissues based on medical images and their related gene expression data.

This invention relates to the field of biotechnology, specifically disclosing an aging biomarker capable of marking cellular senescence and its applications. The purpose of this invention is to provide a novel biomarker for assessing cellular senescence and its applications, aiming to address the problem of the lack of highly specific biomarkers for the senescence status of immune cells in tumor tissues in existing technologies, particularly the technical bottleneck of accurately assessing the degree of immune cell senescence in the complex tumor microenvironment.

The invention belongs to the technical field of biological medicines, and discloses an engineered bacterium for in-situ expression of a microtubule inhibition protein in a tumor and application of the engineered bacterium. The engineering bacteria are formed by constructing microtubule inhibition protein genes to an expression vector and finally transferring the expression vector into bacteria. The engineering bacterium can be colonized in a tumor microenvironment in a targeted manner, expresses microtubule inhibition protein, effectively inhibits tumor cells and remarkably inhibits solid tumor growth, and is excellent in safety.

The present application relates to the field of biomedical technology, and discloses an immune infiltration desert tumor benefit ICI treatment method based on a weighting strategy. The method obtains spatial transcriptome data of tumor tissue of a patient, divides the tumor microenvironment into functional regions through an adaptive grid division algorithm, and extracts a multi-scale feature vector; calculates dynamic weight coefficients of each functional region using a graph attention network, and generates a comprehensive response index after weighted integration; and finally outputs an individualized ICI treatment decision according to the comparison result of the index and a preset threshold. The present application realizes dynamic evaluation of tumor microenvironment heterogeneity based on spatial transcriptome data, and provides ICI treatment response prediction and clinical decision support for patients with immune infiltration desert tumors.

This invention relates to the interdisciplinary field of cell biology, experimental oncology, and translational medicine, specifically to a cancer-associated fibroblast cell line, its construction method, and its applications. This invention fills the research gap in mouse-derived oral squamous cell carcinoma-associated fibroblast cell line models and provides a method for constructing such a cell line. Through the inverted adherent culture and enzymatic digestion methods of this invention, a mouse-derived oral squamous cell carcinoma-associated fibroblast cell line with a clear origin, high purity, and long-term phenotypic and functional stability can be obtained. This allows for the establishment of a cryopreservable and resuscitable mouse oral squamous cell carcinoma-associated fibroblast cell bank, providing technical support for research related to the tumor microenvironment and immunotherapy.

This invention belongs to the field of biomedical technology, specifically relating to a Terminalia chebula active polypeptide, its preparation method, and its application. The preparation method uses Terminalia chebula slices as raw material, which are pulverized, homogenized with water, and then subjected to a series of enzymatic hydrolysis steps: a first hydrolysis with neutral protease, a second hydrolysis with pepsin, and a third hydrolysis with trypsin. Enzyme inactivation is performed after each hydrolysis. Subsequent steps include filtration, removal of alkaline proteins, ultrafiltration, and fine filtration to obtain the Terminalia chebula active polypeptide. The preparation method of this invention, through a three-step progressive enzymatic hydrolysis method, can efficiently prepare highly active Terminalia chebula polypeptides. The obtained Terminalia chebula active polypeptides have small molecular weight, are easily absorbed, and are non-toxic. These active polypeptides exhibit significant anti-tumor and liver fibrosis-improving effects, effectively reshaping the tumor microenvironment, enhancing anti-tumor immune responses, and repairing liver tissue damage. They have broad application prospects in the preparation of anti-tumor and liver fibrosis-improving drugs.

Microscopy imaging that allows for multiple mRNAs, proteins and metabolites to be spatially resolved at a subcellular level provides valuable molecular information which is a crucial factor for understanding tissue heterogeneity as for example within the tumor micro environment. The current invention describes a method (High Density-SUMI-Seq) which combines the use of Spatial Unique Molecular Identifier in situ localization and identification (by in situ sequencing or sequential fluorescence hybridization) of rolonies derived from rolling circle amplification of circular oligonucleotides and in vitro sequencing of target amplified RNA or DNA in combination with SUMI identification at a subcellular level with no optical diffraction limitation in the amount of amplified target information that can be analyzed per cell. Apart from amplified RNA or DNA, the High Density-SUMI-Seq method can also be applied using linear oligonucleotides to spatially resolve proteins and metabolites to provide multiomics results.

The present application relates to the technical field of biomedical sensing, and discloses a tumor microenvironment multi-parameter monitoring method, device, medium and equipment, the method comprising applying an excitation magnetic field to a magnetic nano-probe in a target region, using a photomagnetic probe array to collect a nonlinear magnetization response signal; performing harmonic decomposition and feature extraction on the nonlinear magnetization response signal to obtain a harmonic feature vector for characterizing the nonlinear magnetization response; inputting the harmonic feature vector into a physical constraint inversion engine to solve, simultaneously decouple and output quantitative estimation values of at least two tumor microenvironment parameters of the target region, the at least two tumor microenvironment parameters being any two or more of a pH value, an oxygen partial pressure, a local temperature and a magnetic nano-probe concentration; the physical constraint inversion engine is constructed based on a Bayesian inference framework fused with a physical constraint regularization term. The above method realizes simultaneous, high-precision, in-situ decoupling and monitoring of multiple parameters in a tumor microenvironment.

The application relates to the field of biological medicine, and discloses an active oxygen response thione aldehyde linker as well as a preparation method and application thereof. The thione aldehyde linker structure is a thione aldehyde structure with a p-hydroxyphenyl as a center. The thione aldehyde carbon atom is connected with two -CH2CH2COOH groups through a sulfur atom. The preparation method of the active oxygen response thione aldehyde linker comprises the following steps: dissolving 3-mercapto propionic acid and p-hydroxybenzaldehyde in ethyl acetate, adding trifluoroacetic acid as a catalyst, stirring and reacting at room temperature, and after the reaction is completed, the thione aldehyde linker is obtained through separation and purification. The thione aldehyde linker can respond to the increased ROS level in a tumor microenvironment, is broken under a high ROS condition, and thus realizes the release of a drug molecule connected therewith, which is beneficial to realizing the specific release of the drug at a tumor site.

Disclosed herein are polypeptides and polypeptide complexes that are capable of binding tumor cell antigens and effector cell antigens. In some embodiments, the polypeptides and polypeptide complexes bind the tumor cell antigens and the effector cell antigens in a tumor microenvironment.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

Provided herein is a noninvasive method for measuring pH, glucose and glycogen levels using a single acquisition method, as well as systems for performing the method. This method for glycogen / glucose (and pH) detection has high specificity enabled by superior chemical shift separation in high-strength magnetic fields. The methods have applications in detecting changing tumor microenvironments in cancerous cells for measuring important metrics for noninvasive and quantitative metabolic profiling.

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

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.

This invention belongs to the field of biomedical technology, specifically disclosing a nanomicelle FluDox-MIC, its preparation method, and its uses. This nanomicelle is formed by the self-assembly of flumatinib and doxorubicin co-loaded in mPEG-DSPE, exhibiting pH-responsive release properties. Upon entering the tumor microenvironment, it releases the drug. The released flumatinib induces the degradation of the poliovirus receptor (PVR / CD155), relieving its inhibitory signal on NK cells and reactivating innate immune surveillance. Simultaneously, low-dose doxorubicin induces significant immunogenic cell death (ICD), initiating and amplifying tumor-specific T cell-mediated adaptive immunity. Through the synergistic activation of innate and adaptive immunity, the nanomicelle of this invention can effectively inhibit melanoma growth and overcome immunotherapy resistance, showing promising clinical application prospects.

The application belongs to the field of biological medicine, and provides a tumor microenvironment responsive nano-drug, which comprises a ferrous metal organic framework, polyethylene glycol / leafy on the modified ferrous metal organic framework and PK11195 encapsulated in the metal framework, and a structural formula of the PK11195 is as shown below. The application also provides a preparation method of the tumor microenvironment responsive nano-drug. The application also provides the use of the tumor microenvironment responsive nano-drug in the preparation of a drug for treating hepatocellular carcinoma. The nano-drug can be actively targeted to tumor cells by combining with folate receptors, under the guidance of MRI, and rich ROS is generated by the irradiation of near-infrared light, so as to induce cell ICD, which provides a prospect for promoting systemic antitumor photodynamic therapy and immunotherapy.

This invention belongs to the field of DNA hydrogel technology, specifically relating to a VEGF-responsive, on-demand release smart DNA hydrogel of glycyrrhizin, its preparation method, and its applications. This invention constructs a VEGF-responsive smart DNA hydrogel, efficiently encapsulating glycyrrhizin within a three-dimensional gel network, utilizing the high expression of VEGF in the tumor microenvironment to trigger on-demand drug release. This invention achieves precise on-demand release of glycyrrhizin, significantly improving drug utilization efficiency and reducing systemic toxicity. Simultaneously, the VEGF aptamer introduced into the system can specifically bind to and neutralize free VEGF, blocking angiogenesis, cutting off tumor nutrient supply, and further inhibiting tumor proliferation and progression, achieving a synergistic effect of intelligent drug delivery and anti-angiogenesis.

The application discloses a preparation method of a novel hierarchical drug release lemon exosome nano preparation and application thereof in brain glioma treatment and belongs to the field of nano medicines. The method comprises the following steps: extracting and purifying lemon exosomes, introducing an anti-glioma drug and a first part of LRP1 up-regulating agent into the inner cavity of the exosomes through electroporation, instantaneously constructing a tumor microenvironment responsive nanogel core to fix the drug, embedding a second part of LRP1 up-regulating agent into the lipid layer of the exosome, modifying Angiopep-2 to realize brain targeting, and obtaining the nano preparation through purification. The preparation has the hierarchical drug release characteristics of outer layer early release and inner cavity delayed release, can improve the efficiency of drug crossing the blood-brain barrier and accumulation at the tumor site, enhance the anti-glioma effect, solves the technical problem that the existing drug loading system is difficult to realize multi-drug phased release, and provides a new strategy for brain glioma treatment.

The application discloses a double-drug self-enhanced layered double hydroxide nanosystem and application thereof. The iron-ruthenium layered double hydroxide in the nanosystem has double enzyme activity, can efficiently catalyze H2O2 to generate O2 and active oxygen in a tumor microenvironment, significantly relieves hypoxia while inducing oxidative stress, the MCT4 specific inhibitor VB124 in the system creates an acidic microenvironment by blocking lactic acid output, amplifies the catalytic efficiency of FeRu, and establishes a self-enhanced catalytic effect; and the co-loaded epigenetic regulator JQ1 down-regulates the expression of PD-L1 by inhibiting BET protein. The system amplifies the catalytic efficiency of FeRu, significantly induces ferroptosis, reverses the immunosuppressive microenvironment with the help of epigenetic regulation, induces the release of damage-associated molecular patterns, causes the infiltration of immune cells, and finally cooperatively triggers a strong anti-tumor immune response. The self-enhanced catalysis-epigenetic regulation synergistic strategy realized by the system provides an innovative solution for improving the effect of tumor immunotherapy.

This invention relates to a pH-responsive multifunctional nanoplatform M@FNPs, a drug-loaded composition MP@FNPs, its preparation method, and its applications, belonging to the fields of nanomaterials and biomedical materials technology. The preparation method of the pH-responsive multifunctional nanoplatform M@FNPs includes the following steps: in-situ doping of ZIF-8 with ferric ions during synthesis to obtain iron-doped ZIF-8; dissolving magnesium peroxide nanoparticles and iron-doped ZIF-8 in a solvent; ultrasonicating to load the magnesium peroxide nanoparticles onto the iron-doped ZIF-8; and drying to obtain the final product. The MP@FNPs of this invention, by integrating pH-responsive release, self-supply of hydrogen peroxide and oxygen, and continuous GSH depletion functions, can specifically activate a self-maintaining cascade reaction in the tumor microenvironment, disrupting the redox homeostasis of tumor cells and inducing ferroptosis, thereby effectively overcoming the resistance of tumor cells to platinum-based drugs and synergistically enhancing the efficacy of chemotherapy-immunotherapy.

Provided are compositions and methods for treating cancers, in particular those characterized with PSMA expression such as prostate cancer. The compositions include a conditionally-activatable XTENylated Protease-Activated bispecific T Cell Engager targeting PSMA (PSMA-XPAT) that remain inactive until activated by proteases present in tumor microenvironment. The PSMA-XPAT exhibited exceptional safety profiles even at high doses and were efficacious in cancer patients resistant to even multiple lines of prior therapies.

The present invention provides, among other things, a masked cytokine comprising an interleukin 2 (IL-2) polypeptide, a VHH masking moiety, an anti-PD1 targeting moiety, and an engineered Fc domain comprising a tumor-associated protease cleavage site. In such masked cytokine, the IL-2 polypeptide is engineered to be activatable by a protease at a target site, such as in a tumor microenvironment. The VHH masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e g masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavage site in the Fc domain, the IL-2 polypeptide becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

This invention discloses a high-load XOR tumor-targeting therapy nanoplatform based on ROS activity and its applications, belonging to the field of nanobiomaterials. This high-load XOR tumor-targeting therapy nanoplatform, using a zeolite imidazole framework-8 (ZIF-8) as a carrier, contains xanthine oxidoreductase (XOR) with cellular enzymatic activity. It possesses the ability to target tumor cells and induce intracellular reactive oxygen species (ROS), leading to tumor cell death. Induction of intracellular ROS in tumor macrophages (TAMs) also supports the differentiation of macrophages into M1 types. ROS-induced apoptosis in tumor cells produces a series of tumor-associated antigens, which further promotes the infiltration and activation of macrophages in the tumor microenvironment. This, in turn, leads to increased infiltration of CD8+ T cells in the tumor, whose cytokine profile shows cytotoxic effects, indicating successful induction of an adaptive anti-tumor response. This novel nanomaterial offers a promising new strategy for the immunotherapy of gastric diseases.

This invention discloses a protein-degrading DNA material, its preparation method, and its applications. The protein-degrading DNA material includes a degradation initiation module, a protein targeting module, and a response module. The degradation initiation module is an E3 ubiquitin ligase targeting module, and the response module is a telomerase response module. The preparation method includes the following steps: dissolving the ssDNA strand used in the degradation initiation module in a solvent and annealing it to obtain the degradation initiation module; dissolving the ssDNA strand used in the protein targeting module in a solvent and annealing it to obtain the protein targeting module; dissolving the ssDNA strand used in the response module in a solvent and annealing it to obtain the response module; and mixing the degradation initiation module, the protein targeting module, and the response module to obtain the protein-degrading DNA material. The protein-degrading DNA material of this invention possesses tumor microenvironment triggering characteristics, can precisely target tumor cells, and has a high efficiency in degrading pathogenic proteins.

The application discloses an MMP-2 responsive targeted brain glioma synergistic diagnosis and treatment and immune activation nano probe and a preparation method and application thereof, and relates to the technical field of biological medicine. The probe is formed by assembling an Angiopep-2 targeting peptide, an MMP-2 response sequence, a chemotherapeutic drug and a photosensitizer I-BODIPY, has a hydrodynamic diameter of 10-50 nm, and has excellent biocompatibility. The probe is combined with an LRP1 receptor through the Angiopep-2 to cross the blood-brain barrier, is specifically cut by MMP-2 in a tumor microenvironment to release drugs at a fixed point, integrates the functions of chemotherapy, photothermal / photodynamic therapy and fluorescence imaging, synchronously activates immunogenic cell death and paraptosis, and reshapes an anti-tumor immune microenvironment. The probe can realize precise targeting of brain glioma, synergistic diagnosis and treatment, immune activation and tumor staging evaluation, significantly prolongs the survival period of tumor-bearing mice, and provides a new scheme for glioblastoma diagnosis and treatment.

The present application relates to a kind of unsaturated fatty acid loaded drug delivery system and its preparation method and application, the drug delivery system includes liposome and unsaturated fatty acid loaded in liposome and polymer particle wrapped in the core of liposome;The components of the polymer particle include PC7A polymer and Poly (I:C) polymer.The drug delivery system can efficiently deliver unsaturated fatty acid molecules, greatly increase the content of active molecules of unsaturated fatty acid in cell, improve the efficiency of unsaturated fatty acid into cell, while showing excellent tumor microenvironment regulation ability, improve the efficiency of anti-tumor immunotherapy.

The application discloses a kind of nucleic acid nano vesicles based on sulfonium copolymerization peptide and its preparation method and application.The vesicle is formed by the electrostatic self-assembly of a kind of sulfonium copolymerization peptide and polynucleotide, and is stable nano vesicle with hollow structure.The vesicle is different from conventional solid nanoparticles, and its unique hollow structure provides space for co-loading other therapeutic agents (such as enzymes, chemotherapeutic drugs).The application also provides a preparation method of the nano vesicle, and its application as a carrier for simultaneously loading nucleic acid drugs and other active ingredients for synergistic treatment.The nano vesicle has extraordinary long-term storage stability, and can deliver siRNA and catalase to tumor sites, block CD47 "don't eat me" signal through gene silencing, and enzymatically degrade immunosuppressive factor H2O2 in tumor microenvironment, thereby remodeling tumor immune microenvironment, efficiently activating macrophages, dendritic cells and T cells, and producing strong synergistic anti-tumor immune effect.

This invention relates to the fields of microbiology and biomedicine, and particularly to a strain of *Lactobacillus brittlemi* SYSU-32 and its application in tumor treatment. This invention cultured and isolated a strain of *Lactobacillus brittlemi* (SYSU-32). Limosilactobacillus pontis SYSU-32 was deposited on September 15, 2025, at the China General Microbiological Culture Collection Center (CGMCC), with accession number CGMCC No. 35919. This strain can increase CD8+ in the tumor microenvironment. + Infiltration of T cells and cytotoxic T cells inhibits the progression of colorectal cancer. Furthermore, the combination of *Lactobacillus bridgedii* SYSU-32 with the chemotherapy drug oxaliplatin enhances the pro-apoptotic effect of oxaliplatin, further inhibiting tumor progression and metastasis.