13 results about "Tumor microenvironment" patented technology

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 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 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.

The present application relates to a kind of anti-PD-L1 and HHLA2 bispecific antibody and its preparation method and application.The bispecific antibody includes PD-L1 binding domain and HHLA2 binding domain, the PD-L1 binding domain includes anti-PD-L1 monoclonal antibody, the HHLA2 binding domain includes the variable region of anti-HHLA2 nanobody;The variable region of anti-HHLA2 nanobody is connected with the N terminal or C terminal of the light chain or heavy chain of anti-PD-L1 monoclonal antibody by flexible linker.The present application constructs specific structure anti-HHLA2 and PD-L1 bispecific antibody, with high specificity and affinity, can up-regulate cell-mediated immune response, and enhance the function of T cell and NK cell in tumor microenvironment.In addition, bispecific antibody drug conjugate can be further developed, with higher efficient tumor cell specific killing ability, provide new method, new idea for treating tumor and infectious disease.

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.

This invention provides a method and application for evaluating tumor drugs based on PBMCs and prostate organoids, belonging to the field of biotechnology. The method includes the following steps: (1) Construction of tumor organoids: pre-treating excised tissue to obtain cell clusters, encapsulating the cell clusters with Matrigel, plate-coating, and adding tumor organoid culture medium for culture; (2) Isolating peripheral blood mononuclear cells; (3) Co-culturing peripheral blood mononuclear cells with tumor organoids to obtain CTL cells; (4) Co-culturing CTL cells with tumor organoids, treating the co-culture mixture with tumor drugs, and judging the efficacy of tumor drugs. The tumor drug evaluation method based on PBMCs and prostate organoids provided by this invention utilizes the fact that tumor organoids can more closely reproduce the tumor microenvironment, and more accurately evaluate the efficacy of anticancer drugs.

This invention relates to a biomarker for predicting treatment response to immunotherapy and a gene prediction model utilizing the same, wherein the gene prediction model utilizing the biomarker is based on the expression patterns of key genes that reveal the characteristics of a patient's tumor-microenvironment, thereby predicting treatment response, thus avoiding unnecessary surgery and determining the optimal treatment regimen.

This invention discloses a piezoelectric nanocomposite for regulating pyroptosis, its preparation method, and its applications, relating to the field of tumor immunotherapy. The composite comprises barium titanate nanocubes, gold nanoparticles assembled on the surface of the barium titanate nanocubes, and thiol-modified polyethylene glycol, endoplasmic reticulum-targeting peptides, and cell-penetrating peptides modified on the surface of the gold nanoparticles and / or the barium titanate nanocubes. This invention utilizes ultrasound to excite the endoplasmic reticulum-targeting nanoprobes in the composite, achieving radio-induced tumor cell pyroptosis immunotherapy based on endoplasmic reticulum-mitochondrial crosstalk. Pharmaceutical compositions containing the composite of this invention, after radio-induced stimulation, effectively inhibit the growth of both primary and distal tumors, and this effect is enhanced when combined with anti-CTLA-4 antibodies, inhibiting tumor recurrence. The composite provided by this invention can reverse the immunosuppressive tumor microenvironment and activate systemic anti-tumor immune responses, possessing significant application value in the field of tumor immunotherapy.

This application provides a recombinant oncolytic virus carrying a PD-1 / RGMb bispecific antibody, its preparation method, and its application. The preparation method includes the following steps: S1: preparing the plasmid pXN2-M51R-GFP; S2: obtaining the PD-1 / RGMb bispecific antibody sequence; S3: amplification of the Mouse PD-1 / RGMb bispecific antibody; S4: restriction enzyme digestion of the pXN2-M51R-GFP vector; S5: ligation of the target gene to the vector and transformation of the ligation system; S6: packaging of the recombinant vesicular stomatitis virus; S7: infection of Vero with the recombinant vesicular stomatitis virus; S8: resuspension and extraction of the target virus. In this application, the oncolytic virus is engineered using viral reverse genetics technology to design and construct a tandem PD-1 / RGMb bispecific antibody, which is then integrated into the vesicular stomatitis virus genome. This strategy aims to simultaneously block the PD-1 / PD-L1, PD-1 / PD-L2, and PD-L2 / RGMb signaling axes, thereby reshaping the immunosuppressive tumor microenvironment and synergistically enhancing the oncolytic virus-induced antitumor immune response.

The application discloses a brain glioma whole slice pathological image intelligent analysis method based on a double-path analysis framework, and specifically comprises the following steps: S1, whole slice image preprocessing, utilizing a channel threshold segmentation algorithm, dividing each whole slice image into different foreground tissue regions and background regions, cutting the foreground tissue regions into a plurality of fixed-size image blocks, extracting a feature vector of each image block, and forming a feature cluster; S2, establishing a dynamic sampling mechanism, utilizing a two-stage attention network to perform dynamic multi-instance learning on the feature cluster of each whole slice image, and finally obtaining slice-level feature representation of the whole slice image; and S3, quantifying tumor microenvironment spatial relationship information, obtaining feature representation of a spatial relationship quantization graph, and splicing the feature representation with the slice-level feature representation in the S2, to obtain a final prediction result. The application improves the prediction efficiency and robustness, and improves medical decision speed and quality.

This invention discloses a cascade-response integrated ultrasound microbubble for diagnosis and treatment, its preparation method, and its applications. From the inside out, it comprises a perfluoropentane phase-change core, a drug-loaded PLGA mesoporous nanoparticle intermediate layer, and a lipid shell modified with folic acid and a transmembrane peptide dual ligand. An MMP-2-responsive peptide chain crosslinking agent is embedded in the lipid layer. This invention utilizes the MMP-2 enzyme in the tumor microenvironment to trigger the outer layer's peeling, exposing the transmembrane peptide for enhanced targeting. Then, ultrasound triggers the core's phase-change explosion to release the drug, achieving a closed-loop "identification-confirmation-treatment" cascade. This microbubble exhibits good stability and high drug delivery efficiency, with a cumulative release rate exceeding 85% after 48 hours under dual stimulation, demonstrating significant in vivo tumor-suppressing effects. This invention provides an intelligent ultrasound microbubble platform for precision tumor diagnosis and treatment.

This invention discloses a depolymerizable carbon dot composite system for enhancing tumor penetration, its preparation method, and its applications, belonging to the field of pharmaceutical technology. Specifically, it relates to the preparation of a carbon dot composite system for enhancing tumor penetration and its application in tumor cascade catalytic therapy and photothermal therapy. The carbon dot composite system consists of iron-doped red-light nanozyme carbon dots, glucose oxidase, and hyaluronic acid to reduce the system's immunogenicity. Through the targeted action of hyaluronic acid on the tumor site, depolymerization occurs in the tumor microenvironment under the influence of hyaluronidase and photothermal heating. Glucose oxidase consumes glucose at the tumor site to produce hydrogen peroxide, thereby generating more hydroxyl radicals and simultaneously performing starvation therapy. This invention's carbon dot composite system for enhancing tumor penetration combines cascade catalytic therapy, photothermal therapy, and starvation therapy to achieve highly efficient tumor growth inhibition, providing an important reference for multimodal tumor treatment.