230 results about "Immune microenvironment" patented technology

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

The invention relates to the technical field of biomedical materials, in particular to engineered small extracellular vesicle hydrogel enriched with PD-L1 and Siglec-15 as well as a preparation method and application of the engineered small extracellular vesicle hydrogel. The engineering small extracellular vesicle hydrogel is enriched with PD-L1 and Siglec-15 at the same time, the engineering small extracellular vesicle hydrogel comprises a hydrogel base body and PDL1-Siglec15-sEVs loaded in the hydrogel base body, and the PDL1-Siglec15-sEVs are small extracellular vesicles with the PD-L1 and the Siglec-15 in an overexpression mode. Compared with natural small extracellular vesicles and a traditional wound surface treatment strategy, the engineered small extracellular vesicle hydrogel has the advantages that PD-L1 and Siglec-15 can be enriched in the vesicles, so that more accurate immune microenvironment regulation and control can be realized on the local part of a wound surface, excessive inflammatory response is moderately inhibited, phenotype transformation of macrophages to be beneficial to tissue regeneration is promoted, and the wound surface treatment effect is improved. The hydrogel is used as a carrier and can provide a moist healing environment and a three-dimensional scaffold structure, so that the residence time of the engineered small extracellular vesicles on the local wound surface is remarkably prolonged, and slow release is realized.

The invention belongs to the technical field of high polymer material synthesis, and particularly relates to an artificial antioxidant enzyme material with an interlayer structure and a preparation method of the artificial antioxidant enzyme material. The preparation method of the artificial antioxidant enzyme material comprises the following steps: dissolving an aldehyde monomer and an amine monomer in a reaction solvent, performing thermal polymerization under the action of an acid catalyst, and then loading interlayer coordination metal, and further defining an aldehyde monomer and an amine monomer as well as an interlayer coordination metal. According to the present invention, the treatment-level oxidation resistance can be achieved through the space-optimized catalysis center and the fully-conjugated frame structure, and the innovative strategy is provided for solving the inflammation-driven tissue damage through the precise oxidation-reduction regulation and the immune microenvironment engineering.

The invention belongs to the technical field of pharmaceutical preparations. The invention discloses a multifunctional bionic nano preparation, a preparation method and application. According to the multifunctional bionic nano preparation, the ginsenoside Rg3 has the dual functions of a medicine and a membrane stabilizer, the platelet membrane has the natural targeting capability on circulating tumor cells and metastases, and meanwhile, the cationic liposome is used for adsorbing negatively-charged NETs nucleic acid protein compounds, so that potential reversal and active targeting are achieved, and the multifunctional bionic nano preparation has a good application prospect. And by co-carrying paclitaxel (PTX) and a photothermal agent (PCP) and integrating photothermal-chemotherapy-immunogenic death (ICD) induction functions, the tumor-related fibroblast activation can be effectively inhibited, circulating tumor cells can be efficiently captured, a tumor immune microenvironment can be remodeled, the tumor cells can be effectively killed, and tumor distal metastasis can be inhibited.

The invention relates to the technical field of biological medicines, in particular to a CKAP4-targeted tumor antigen peptide, a vaccine and application of the CKAP4-targeted tumor antigen peptide. The invention provides a high-immunogenicity tumor antigen peptide RLTELTKSI targeting human and mouse homologous CKAP4 protein, and the tumor antigen peptide and a vaccine thereof can realize efficient killing of CKAP4 positive tumor cells and remarkable inhibition of CT26 subcutaneous tumor by activating specific CD8 + T cell immune response. The traditional single-target limitation is broken through, the co-expression characteristic of CKAP4 in tumor cells and immunosuppressive cells (TAM / TAN) is utilized, a double-target and double-channel mechanism is initiated, and the immunosuppressive state of cold tumors is effectively reversed by inducing T cells to synchronously kill tumor cells and remodel an immune microenvironment. According to the technology, CKAP4 is expanded from an antibody target to a T cell vaccine target, lasting specific CTL response can be stimulated, the off-target risk of antibody treatment is avoided, a universal treatment scheme can be provided for solid tumors, and the clinical transformation potential and the treatment broad spectrum are remarkably improved.

The invention discloses a carbon dot, hydrogel containing the carbon dot as well as a preparation method and application of the hydrogel, and relates to the technical field of carbon materials. The carbon dot is prepared from the following raw materials: a hydroxyl-containing flavonoid compound and epsilon-polylysine; the carbon dots contain aniline bonds formed by hydroxyl groups of the hydroxyl-containing flavonoid compounds and amino groups of the epsilon-polylysine. The carbon dot shows higher tumor cell killing property and lower normal cell toxicity than the raw material hydroxyl-containing flavonoid compound at the cellular level, can obviously induce immunogenic death of cancer cells and does not induce up-regulation of extracellular matrix collagen, and also has a better effect of regulating a tumor immune microenvironment.

The invention discloses a black phosphorus hydrogel microneedle patch loaded with trained mesenchymal stem cells as well as a preparation method and application of the black phosphorus hydrogel microneedle patch, and belongs to the technical field of biological medicines. The micro-needle patch comprises a hydrogel substrate layer loaded with black phosphorus nanosheets and a hydrogel needle tip part for packaging the stem cells. The mesenchymal stem cells are subjected to combined domestication with low oxygen and high active oxygen, so that the anti-oxidative stress, anti-inflammatory and angiogenesis promoting capabilities of the mesenchymal stem cells are remarkably enhanced. After the patch is subcutaneously delivered, the black phosphorus component can efficiently remove bacteria and reduce drug resistance; after being domesticated, the stem cells can adapt to the immune microenvironment of the wound surface, and the immune regulation, inflammation inhibition and tissue regeneration promotion are synergistically realized by continuously releasing anti-inflammatory and angiogenesis promoting factors, so that the refractory wound surface caused by immune disorders such as systemic lupus erythematosus (SLE) and the like is effectively treated. The invention provides an innovative treatment strategy for chronic inflammatory wound healing.

The invention provides a model for predicting lung adenocarcinoma prognosis and immunotherapy response based on copper death related LncRNAs, and belongs to the technical field of bioinformatics. According to the prediction model provided by the invention, the accuracy and the stability of prognosis judgment of a lung adenocarcinoma patient can be remarkably improved, and the defects of a traditional staging system in the aspects of reflecting tumor heterogeneity and individual treatment reaction difference are effectively overcome; the model not only can realize reliable individual risk grading, but also can further evaluate the tumor immune microenvironment state and predict the potential reaction of a patient to immunotherapy, so that a powerful auxiliary tool is provided for clinically formulating an accurate treatment strategy, in particular to the application decision of an immune checkpoint inhibitor; and finally, the method has important practical application value for improving treatment selection and life quality of patients.

The invention relates to antioxidant sonodynamic hydrogel as well as a preparation method and application thereof, the yield and sonodynamic performance of ROS (reactive oxygen species) can be improved, and the prepared hydrogel can realize efficient antibiosis in the early stage of infection, exert antioxidant and repair promoting effects in the later stage of infection, and can promote angiogenesis and collagen deposition, optimize inflammation and immune microenvironment, improve the immunity of the ROS and improve the ROS yield and the sonodynamic performance of the ROS. The dynamic balance of antibiosis, antioxidation and healing promotion is realized, and the treatment effect is comprehensively improved.

The invention provides an allosteric nanogel adjuvant as well as a preparation method and application thereof, and belongs to the technical field of vaccines. The allosteric nanogel adjuvant comprises a self-assembly motif, a responsive site and an immunomodulatory peptide fragment, and the self-assembly motif is composed of 2-5 amino acids; the allosteric nanogel adjuvant has a structure as shown in a formula I, and is named as NTP5 for short; the allosteric nanogel adjuvant is self-assembled into nanoparticles, the nanoparticles are allosteric into a nanofiber structure through responsive broken bonds, nanogel is further formed, and the key problems of a traditional vaccine in the aspects of antigen delivery and immune activation are effectively solved. The nanogel adjuvant can efficiently load various antigens to form a stable nano vaccine, activate an immune microenvironment and provide more means and thoughts for vaccine development.

The application discloses application of DUSP4 in preparation of a marker for predicting the curative effect of immunotherapy of hepatocellular carcinoma and a sensitizing drug, and belongs to the technical field of biological medicine.The application finds that high expression of dual specificity phosphatase 4 (DUSP4) is significantly related to high response rate and long survival period of an immunological checkpoint blocking therapy for a hepatocellular carcinoma patient.DUSP4 promotes CD8+ T cell and NK cell infiltration and remodels an immune microenvironment by inhibiting a TGF-beta signal path, down-regulating an immunosuppressive factor and up-regulating an antigen presenting molecule and a chemotactic factor.The application provides a kit and a method for detecting the expression level of DUSP4 to predict an immunotherapy response, and a combined drug composition comprising a DUSP4 activator or a TGF-beta inhibitor and an immunological checkpoint inhibitor.Experiments prove that up-regulation of the expression of DUSP4 can significantly enhance T cell killing function, and produces a synergistic anti-tumor effect with an anti-PD-1 antibody.The application provides a new strategy for precise stratified treatment and overcoming immunological drug resistance of hepatocellular carcinoma.

This invention relates to the fields of biomedical technology and biological model construction technology, and discloses an ANCA-associated vasculitis glomerular endothelial cell injury model, its construction method and application, and the application of BACH1 inhibitors. The method includes: (1) activating neutrophils sequentially with tumor necrosis factor α and immunoglobulin G to obtain a culture medium containing activated neutrophils; wherein the immunoglobulin G is immunoglobulin G isolated and purified from the plasma of patients with ANCA-associated vasculitis; (2) co-culturing the culture medium containing activated neutrophils with human glomerular endothelial cells to obtain the cell injury model. The cell injury model provided by this invention can verify the role of neutrophil adhesion characteristics in endothelial cell injury, and at the same time, the cell injury model can better simulate the immune microenvironment of ANCA-associated vasculitis glomerular endothelial cells in vivo.

The invention discloses a double-target chimeric antigen receptor capable of simultaneously targeting TLL1 and B7H3, a CAR-T cell and application of the double-target chimeric antigen receptor. The chimeric antigen receptor is a fusion protein which is sequentially composed of Omburt-scFv (SEQ ID NO: 1) targeting B7H3, a CD8 alpha hinge region and transmembrane region, a 4-1BB costimulatory domain, a CD3 zeta signal domain and TLL1-scFv (SEQ ID NO: 6) targeting TLL1 from an N terminal to a C terminal. The TLL1-scFv can be efficiently combined with TLL1 protein, can inhibit a TGF-beta signal channel and block prostate cancer cell migration, and is integrated into CAR of targeted B7H3, so that the double-target CAR-T cell with direct killing and immune microenvironment regulation functions is successfully constructed. The CAR-T cell has a remarkable killing effect on a prostate cancer cell line DU145, can be strongly activated after being co-cultured with a target cell and secretes a large amount of IFN-gamma and TNF-alpha, and shows high immunocompetence. The invention provides a new synergistic immunotherapy strategy for the B7H3-positive prostate cancer with the TGF-beta signal channel activated.

The application provides a self-driven BCG-nanoparticle complex and a preparation method thereof, and belongs to the fields of biological medicine and nanomaterials. The complex is a composite of BCG and cerium oxide nanoparticles with urease activity, the cerium oxide nanoparticles are coupled to the surface of the BCG in an asymmetric distribution through modified polyethyleneimine, and specifically, the surface of the BCG is connected to several modified polyethyleneimine derivatives through chemical bonds and electrostatic adsorption, and the polyethyleneimine derivatives wrap the cerium oxide nanoparticles through electrostatic adsorption. The complex can be self-driven by using the gas release and ion concentration change caused by the catalytic decomposition of urea in the environment, significantly enhances the adhesion and retention of BCG on the bladder wall, effectively overcomes the defects of low delivery efficiency and insufficient immune activation of traditional BCG therapy, simultaneously improves the tumor immune microenvironment, and can be used for preparing high-efficiency and low-toxicity bladder cancer treatment drugs.

The application belongs to the technical field of biological medicine, and discloses an in-situ vaccine type mRNA-tLNP preparation for solid tumor treatment and preparation and application thereof. The preparation is designed by double targets, so that CAR-T kills more tumor cells to overcome tumor heterogeneity, changes the tumor immune microenvironment through autocrine fusion proteins (anti-PD-1 scFv and TGFbetaRII, IL-15 and Flt3L, CD40L), promotes T cell proliferation, and recruits and activates dendritic cells, cross-presents new antigens in the tumor local part, and produces in-situ vaccination effects; circular RNA encoding the above proteins is prepared, and the circular RNA is wrapped by lipid nanoparticles modified by CD3 antibodies, so as to be directly delivered to the body, and a significant solid tumor treatment effect is produced.

The invention belongs to the technical field of biological medicines, and particularly discloses a pH and ultrasound double-response type oncolytic microorganism as well as a preparation method and application thereof. On the basis of a tumor targeting platform, a mild thermal response gene loop expression GM-CSF and a surface-coated oncolytic microbial system are integrated, chemotherapeutic drugs are released in a tumor core area, and immunogenic cell death is induced. A thermal response loop is accurately activated through low-intensity focused ultrasound, and engineering bacteria are promoted to express GM-CSF and secrete a large amount of mannose modified OMVs. Due to the nanometer size and mannose targeting of the OMVs, the OMVs are efficiently enriched in lymph nodes, the OMVs are reprogrammed into an immune activation state from an immune tolerance state, and the OMVs and ICD cooperate to promote dendritic cell maturation, tumor antigen presentation and activation of tumor killer T cells, so that a remarkable and powerful treatment effect is achieved in various tumor models, and the application prospect is wide. A new strategy is provided for remodeling the lymph node immune microenvironment and enhancing the anti-tumor immune response.

This application relates to the fields of chemistry and biomedicine, specifically to a tofenamic acid lipid composition, its preparation method, and its application. A tofenamic acid derivative is obtained by reacting a morpholine solution with tofenamic acid, ethyldimethylaminopropylcarbodiimide, and 4-dimethylaminopyridine, followed by purification. The morpholine in the morpholine solution is an N-alkylmorpholine compound. The tofenamic acid derivative is used to prepare tofenamic acid prodrug liposomes via ethanol injection, which are then used in combination with a STING agonist. The synergistic effect of the combined treatment stems from the dual regulation of the tumor immune microenvironment (TME), overcoming the immune escape induced by STING monotherapy. After STING agonist treatment, the intratumoral COX-2 / PGE2 axis is activated, leading to immunosuppression. The combination of tofenamic acid liposomes and a STING agonist inhibits COX-2, thus relieving this negative feedback loop.

The present application relates to the field of pharmaceutical preparation and nanomedicine, and particularly relates to a kind of nano-drug composition, its combined drug delivery system and application.The nano-drug composition comprises alpha 1-AR blocker and amphiphilic nano-carrier;The alpha 1-AR blocker is loaded in the hydrophobic core formed by amphiphilic nano-carrier;The alpha 1-AR blocker is selected from one or more of prazosin, terazosin, doxazosin;The average particle size of the nano-drug composition is 220-260 nm, the polydispersity index is less than 0.3, and the encapsulation efficiency is greater than 50%.The nano-drug composition of the present application has dual functions of anti-tumor proliferation and immune microenvironment remodeling, improves the dispersion stability of the drug in physiological medium, effectively reduces the in vivo clearance rate, prolongs the circulation time, and realizes the efficient in vivo delivery of the drug.The preparation process of the nano-preparation is stable and can be produced on a large scale.

This invention relates to a locally injectable hydrogel for treating pancreatic cancer, its preparation method, and its application. The hydrogel is prepared from raw materials comprising hyaluronic acid-dopamine and a radionuclide. Through extensive research and optimization, this invention has discovered that reacting hyaluronic acid-dopamine and a radionuclide in a suitable temperature and solvent, followed by mixing the resulting reaction solution with an alkaline sodium periodate solution and rapid stirring, successfully prepares a locally injectable hydrogel highly suitable for treating pancreatic cancer. The hydrogel is prepared under mild conditions, has a simple composition, and high safety. It effectively addresses the core bottlenecks in local radiotherapy for pancreatic cancer, such as poor stability of radionuclide carriers, short retention time, and uncontrollable release. Furthermore, it can reshape the body's immune microenvironment and enhance anti-tumor immune responses, significantly improving therapeutic efficacy. This has significant clinical implications for overcoming the current limitations in the treatment of locally advanced unresectable pancreatic cancer.

The present application relates to the technical field of biomedical materials, in particular to an engineered small extracellular vesicle hydrogel enriched with PD-L1 and Siglec-15, and a preparation method and application thereof. The engineered small extracellular vesicle hydrogel is simultaneously enriched with PD-L1 and Siglec-15, and comprises a hydrogel matrix and PDL1-Siglec15-sEVs loaded in the hydrogel matrix, wherein the PDL1-Siglec15-sEVs are small extracellular vesicles overexpressing PD-L1 and Siglec-15. Compared with natural small extracellular vesicles and traditional wound treatment strategies, the engineered small extracellular vesicle hydrogel of the present application can realize more precise immune microenvironment regulation at the local wound by enriching PD-L1 and Siglec-15 in the vesicles, moderately inhibit excessive inflammatory response, promote the phenotype transformation of macrophages to a phenotype conducive to tissue regeneration, help smooth transition from the inflammatory stage to the proliferation and reconstruction stage, and the hydrogel as a carrier can provide a moist healing environment and a three-dimensional scaffold structure, significantly prolong the residence time of the engineered small extracellular vesicles at the local wound, and realize slow release.

The application discloses a kind of nanomaterial and its preparation method and application, the nanomaterial includes exosome and liposome;The exosome expresses immune checkpoint, the exosome is derived from brain glioma cell;The liposome is loaded with I type photosensitizer.The application is by PDT, immune checkpoint and brain glioma cell exosome antigen three tubes simultaneously to remodel tumor local immune microenvironment, greatly improve the efficiency of cancer immunotherapy, can activate strong anti brain glioma immune response and overcome immune escape.

This invention discloses a T-cell training method based on tumor organ-on-a-chip. The method includes: preparing an organ-on-a-chip with a micropillar array and a biomimetic fishbone structure; introducing primary tumor cells from a patient into the chip, causing them to spontaneously form uniform three-dimensional tumor spheroids; dynamically pumping pre-activated peripheral blood lymphocytes from the same patient into the chip and co-culturing them with the tumor spheroids; collecting the co-cultured lymphocytes and repeating the co-culture process multiple times to obtain a lymphocyte population with enhanced anti-tumor activity. This invention utilizes organ-on-a-chip technology to highly simulate the dynamic tumor immune microenvironment in vivo. Through multiple cycles of "training," it effectively activates and expands tumor-specific T cells, avoiding immune exhaustion, and providing a highly efficient and controllable new platform for personalized immunotherapy of solid tumors.

The present application relates to the application of Hhex agonists in promoting anti-tumor immunity. Specifically, the present application provides a pharmaceutical composition comprising chenodeoxycholic acid and an anti-PD-1 antibody. The present application also provides the use of chenodeoxycholic acid and an anti-PD-1 antibody in the preparation of a drug for promoting anti-tumor immunity. In addition, the present application also provides the use of chenodeoxycholic acid and an anti-PD-1 antibody in the preparation of a drug for treating tumors. The present application uses chenodeoxycholic acid to improve the tumor immune microenvironment and uses it to treat subcutaneous tumors, further verifying that the application of chenodeoxycholic acid can improve the tumor immune microenvironment.

The present application relates to the field of liver cancer immunotherapy efficacy evaluation method combining imageomics and deep learning, and specifically discloses a liver cancer immunotherapy efficacy evaluation method combining imageomics and deep learning. The method comprises the following steps: acquiring multi-modal medical images and clinical information of a liver cancer patient; performing standardization preprocessing and automatic lesion segmentation on the images; extracting features through a multi-scale deep network and realizing semantic alignment by using a cross-modal attention mechanism; fusing the images and the clinical data to construct a multi-source heterogeneous feature matrix; adopting a hierarchical model structure, modeling the spatial distribution of tumor immune microenvironment by using a graph neural network at the bottom layer, dynamically tracking the evolution of efficacy by using a gated recurrent unit at the upper layer, and finally outputting an immune response probability, a tumor load trend and a treatment response grade. The present application can objectively and quantitatively evaluate the efficacy of liver cancer immunotherapy, and improve the precision and automation level of individualized diagnosis and treatment decision-making.

The invention relates to the technical field of biological medicines, and aims to provide a novel application of bifidobacterium breve in preparation of a medicine for preventing and / or treating melanoma, and the purpose of preventing and treating melanoma is achieved by changing the immune microenvironment of melanoma by using microorganisms.

This invention provides a hypoxia-mediated mechanism of malignant tumor formation, a treatment simulation method, and a system, relating to the field of biomathematical modeling technology. The method includes: dividing the tumor into a core region and a peripheral region, defining the core differences between the two regions in their microenvironmental composition, and forming a conceptual interaction network; establishing a state variable system centered on the number of tumor cells, constructing a mathematical model integrating tumor core-periphery heterogeneity, hypoxia-mediated processes, and immunosuppression cycles; solving the mathematical model, calculating the changes of each state variable over time under different initial conditions or intervention parameters, and outputting simulation results characterizing tumor growth and the state of the immune microenvironment; this invention, through the multi-level regulation of cell proliferation, immunosuppression cycles, and angiogenesis signals by oxygen concentration gradients, more realistically reproduces the spatial heterogeneous growth dynamics of solid tumors in vivo, and simulates the formation and maintenance mechanism of a strong immunosuppressive state in the tumor core region.

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 application of raspberry ketone in the immunotherapy of pancreatic cancer belongs to the technical field of biological medicine, and provides the application of raspberry ketone in the immunotherapy of pancreatic cancer. The application discloses that raspberry ketone can specifically and widely up-regulate the expression of MHC-I molecules on the surface of pancreatic cancer cells, and significantly enhances the infiltration and function of anti-tumor effector T cells in the tumor immune microenvironment. In-vivo and in-vitro experiments prove that raspberry ketone can reverse tumor immune escape by up-regulating MHC-I, and after being combined with a PD-1 immune checkpoint inhibitor, the raspberry ketone can produce a significant synergistic anti-tumor effect, significantly inhibit the growth of pancreatic cancer and prolong the survival period of tumor-bearing mice. The application provides a new strategy of combining a natural small molecule immunomodulator with an existing immunotherapy, and provides an innovative solution and a drug candidate for overcoming the difficulty of pancreatic cancer tolerance to immunotherapy.

The invention discloses a multi-target self-assembly cyclic peptide with tumor microenvironment regulation and control, belongs to the technical field of nano medicine, and aims to solve the problems of short blood vessel normalization period, inconsistent action time of combined medicines and the like in a traditional clinical combined treatment scheme. The self-assembly cyclic peptide comprises a TIGIT blocking unit, a self-assembly unit and a blood vessel regulation and control targeting unit which are connected in sequence, the blood vessel regulation and control targeting unit comprises a Tie2-VEGF targeting fragment and a corner structure fragment, and the Tie2 targeting fragment, the VEGF targeting fragment and the corner structure fragment are coupled through disulfide bonds to form an annular peptide. The synthesized multi-target self-assembly cyclopeptide can be quickly self-assembled to form a nanofiber network with a beta-folding structure after being enriched at a tumor site, and the nano reticular supramolecular assembly structure has the effects of strong combination and long-acting retention at a target protein, so that the functions of long-acting blocking and regulation and control of tumor blood vessels and immune microenvironment are achieved.

This invention belongs to the field of biomedical materials technology, specifically disclosing a core-shell microneedle, a core-shell microneedle patch, its preparation method, and its application. Through structural design and carrier material optimization, this invention provides a core-shell microneedle with a programmed sequential release of tannic acid in the outer shell and verteporfen in the core layer, successfully matching the dynamic physiological rhythm of wound healing and ensuring effective wound repair. In vitro and in vivo biological evaluations have confirmed that the core-shell microneedle patch prepared using the core-shell microneedles of this invention possesses excellent antibacterial, antioxidant, and immune microenvironment-regulating abilities. It can effectively induce macrophage polarization towards the M2 type, specifically inhibit YAP protein expression, and significantly accelerate the closure process of infected wounds. From both upstream immune regulation and downstream fibrosis inhibition levels, it dually blocks the pathological scar formation pathway, ultimately achieving high-quality, scar-free regenerative repair of infected wounds.