120 results about "CD44" patented technology

The invention discloses a tumor cholesterol metabolism regulation microneedle patch and a preparation method, the microneedle patch comprises a needle tip and a backing which are connected, the needle tip comprises a needle tip body and nanoparticles loaded on the needle tip body, the nanoparticle is a manganese ion-doped organic metal framework, the outer layer of the manganese ion-doped organic metal framework is modified with a targeting agent, cholesterol oxidase and superoxide dismutase are carried on the manganese ion-doped organic metal framework, the targeting agent can target a CD44 receptor, and the organic metal framework can carry drugs. The targeted drug can enter tumor cells in a targeted mode, superoxide dismutase catalyzes superoxide anions overexpressed in the tumor cells to generate H2O2 and O2, O2 needed by catalysis is provided for cholesterol oxidase, cholesterol at the tumor site is consumed by the cholesterol oxidase, accumulation of 7-DHC is reduced, meanwhile H2O2 can be generated, and the cholesterol oxidase can be used for catalyzing the tumor site. H2O2 is catalyzed by manganese ions through a Fenton-like reaction to generate OH to induce tumor cells to generate ferroptosis, so that ferroptosis-immune synergistic treatment is realized.

The invention belongs to the technical field of nano material synthesis, and particularly relates to baicalein-copper nano microgel as well as a preparation method and application thereof. According to the invention, copper ions and baicalein are coordinated to form nanowires, and the nanowires are coated with hyaluronic acid (HA) to prepare the nano microgel. The method is carried out at normal temperature, is simple in process and high in yield, and does not need toxic solvents; the obtained microgel has high stability (gastric acid resistance), targeted delivery (CD44 receptor mediation) and multiple biological activities (oxidation resistance and inflammation resistance). Animal experiments show that the pharmaceutical composition can significantly relieve ulcerative colitis, the dosage is as low as 5 mg / kg, the pharmaceutical composition is non-toxic, and a new strategy is provided for treatment of inflammatory diseases.

The invention discloses an efficient targeting anti-hepatic fibrosis nano drug delivery system and a preparation method thereof. According to the system, a pentacyclic triterpenoid compound lupeol extracted from cichorium glandulosum is taken as an active ingredient, and the hyaluronic acid modified ZIF-8 loaded lupeol nano drug delivery system (HA / Lupeol ZIF-8) is constructed aiming at the problems of poor water solubility, low stability, weak targeting property and the like of the pentacyclic triterpenoid compound lupeol. The system is synthesized by a room-temperature solution method, hydrophobic lupeol is efficiently entrapped by using a porous structure of ZIF-8, and active targeting of a CD44 receptor on the surface of the hepatic stellate cell is realized by surface modification of hyaluronic acid. The particle size of the nano drug delivery system is 50-200nm, the encapsulation efficiency is 97.4%, and the drug loading capacity is 23.8%. In a fibrotic acidic microenvironment, the ZIF-8 carrier can responsively degrade and release a drug, and effectively penetrates through a collagen deposition barrier, so that precise drug delivery is realized. According to the invention, a new strategy is provided for anti-hepatic fibrosis treatment by combining degradation of ZIF-8 in a hepatic fibrosis acidic microenvironment and active targeting bifunctional characteristics of hyaluronic acid for the first time.

The invention belongs to the technical field of medicines, and discloses preparation and application of a paclitaxel-loaded liposome nano targeting preparation. The paclitaxel-entrapped nano-particles are prepared by adopting a film dispersion method, and micromolecular hyaluronic acid is entrapped on the surfaces of the lipid nano-particles by utilizing the charge effect. The bionic nano-drug provided by the invention is helpful for solving the problems of poor solubility, low bioavailability, high toxicity and the like of the anticancer drug paclitaxel. The hyaluronic acid has affinity with a glycoprotein CD44 receptor on the surface of a tumor cell, so that the nanoparticles are targeted and concentrated at a tumor part, the anti-tumor effect is improved, and the systemic toxicity of paclitaxel is reduced. The preparation process is simple, the cost is low, the stability is good, the repeatability is high, and the preparation method also has a better development prospect in the aspect of clinical application transformation.

The invention relates to the technical field of hyaluronic acid derivatives and nano drug delivery systems, in particular to a lipoic acid grafted hyaluronic acid derivative, a preparation method and application, and provides a lipoic acid grafted hyaluronic acid derivative with a structure that lipoic acid is grafted with hyaluronic acid through a thioketal bond. A lipoic acid grafted hyaluronic acid derivative loaded IAA drug delivery system is constructed, can be gathered at a colitis disease part through intravenous injection, and is actively absorbed by cells by virtue of the affinity effect of hyaluronic acid in a lipoic acid grafted hyaluronic acid derivative structure on CD44 receptors on the surfaces of inflammatory cells; according to the present invention, with the application of the IAA in the cell, the responsive structure degradation occurs in the intracellular high oxidative stress environment, and the IAA is delivered into the cell in the positioning manner, such that the IAA inhibits the inflammation generation by activating the AhR and the downstream oxidative stress and inflammatory reaction related pathway so as to promote the mucous membrane repair, and the problem that the colitis treatment drug cannot accurately act on the focus in the prior art is solved.

The invention belongs to the technical field of biological medicine, and particularly relates to a CD44 / GSH dual-response eutectic drug delivery system and a preparation method thereof.The CD44 / GSH dual-response eutectic drug delivery system comprises a microneedle array composed of a biodegradable polymer matrix formed by hyaluronic acid (HA) and poly (lactic-co-glycolic acid) (PLGA), and the microneedle array comprises a plurality of microneedles; a microneedle comprising a pharmaceutical formulation of a resveratrol-berberine co-crystal integrated into the polymer matrix; wherein the polymer matrix comprises a disulfide bond that is a glutathione (GSH) responsive switch; wherein the hyaluronic acid is capable of specifically targeting a CD44 receptor; wherein the disulfide bond can be cleaved under the condition that the concentration of glutathione in a target tissue is increased, thereby releasing the resveratrol-berberine eutectic pharmaceutical formulation; and wherein the microneedle array is configured to percutaneously deliver the resveratrol-berberine co-crystal pharmaceutical formulation to the target tissue.

The invention relates to the technical field of liposome preparation, and particularly discloses a nano liposome and a preparation method thereof.The method comprises the steps that distearoyl phosphatidyl ethanolamine, cholesterol, hydroxyl-terminated polyethylene glycol and mPEG-Hyd-PEG-SH are dissolved in a mixed solvent, and a lipid film is formed through rotary evaporation; hydrating with a PBS (Phosphate Buffer Solution) containing ammonium sulfate, and carrying out ultrasonic treatment to obtain primary emulsion; a doxorubicin solution is added for incubation, and drug loading is completed; the CD44 antibody and the drug-loaded liposome are coupled in a catalytic system, and are homogenized by a spiral microreactor. The problems of high immunogenicity, insufficient targeting, non-uniform particle size, uncontrollable drug release and complex preparation process of the existing PEG nano-liposome are solved, and the PEG nano-liposome has the advantages of low immunogenicity, high targeting, uniform and stable particle size, drug response release and easiness in large-scale production.

Provided are methods and compositions for enhancing radiotherapy in various cancers by administering dopamine receptor (DRD2)‐binding phenylpiperazine derivatives such as brexpiprazole, cariprazine, pipamperone, and perospirone. In vitro studies show that combining these agents with ionizing radiation (e.g., 5 Gy) significantly reduces cancer cell survival, suppresses metastatic and stemness markers (e.g., CD44, MMP‑2, Snail, Nanog), and promotes apoptosis. Fractionated or single‐fraction radiation regimens can be paired with DRD2 antagonists to lower treatment‐resistant phenotypes, decrease the likelihood of recurrence, and potentially reduce necessary radiation dosages. The approach applies to breast, prostate, lung, pancreatic, and brain cancers, among others. Depending on tumor characteristics, additional chemotherapeutic or immunotherapeutic agents may further improve outcomes.

The invention discloses an application of a biomarker in typing of polymorphic glioblastoma, and the biomarker is combined by selecting at least one of the following categories: at least one of a plurality of gene markers for identifying a proliferative type, a protein marker DLL3 and / or Ki67, a protein marker DL3 and / or Ki67, a protein marker DL3 and / or Ki67, a protein marker DL3 and / or Ki67, a protein marker DL3 and / or Ki67, and a protein marker DL3 and / or Ki67. At least one of a plurality of gene markers for identifying the neurosynaptic type, a protein marker GRMM3 and / or FGFR2; at least one of a plurality of gene markers for identifying the metabolic type, a protein marker P16; and at least one of a plurality of gene markers for identifying the immune regulation type, and at least one of protein markers CD44, C1R and Ki67. The application provides comprehensive features of EAS-GBM, and enhances understanding of occurrence, clinical stratification and treatment strategies of different ancestral tumors.

The invention relates to the technical field of biological medicines, and discloses hyaluronic acid modified metal coordination albumin nanoparticles as well as a preparation method and application thereof. The hyaluronic acid modified metal coordination albumin nanoparticle comprises a core and a hyaluronic acid shell layer, wherein the core is formed by self-assembly of an albumin-drug compound, poly-L-aspartic acid and ferric ions through coordination, and the hyaluronic acid shell layer is connected to the surface of the core through coordination or adsorption. According to the hyaluronic acid modified metal coordination albumin nanoparticles as well as the preparation method and the application thereof, the preparation method is simple, convenient and rapid, does not need complex covalent modification, is mild in condition and is easy for large-scale production, and the prepared nanoparticles are uniform in particle size, good in stability and high in stability. In addition, due to the fact that the hyaluronic acid is modified on the surface, the active targeting capacity on CD44 receptor high-expression tumor cells is achieved, the enrichment and treatment effects of the medicine on the tumor site are remarkably improved, and the application prospect in preparation of the anti-tumor medicine is wide.

The application discloses an albumin nano-drug based on HSP90 inhibitor and a preparation method and application thereof, and belongs to the technical field of medicines.The short peptide A6 is modified to human blood albumin through a connecting chain, and the human blood albumin modified by the A6 is self-assembled with geldanamycin derivative G2111 in the presence of an organic solvent, so that the G2111 is combined to the hydrophobic region of the human blood albumin through a non-covalent bond, effective loading of the G2111 is realized, the solubility of the geldanamycin derivative is improved, the drug is targetedly released into cancer cells with high expression of CD44, the targeted accumulation of the drug in tumor tissues is enhanced, damage to other normal tissues and cells caused by off-target effects of the drug is avoided, the albumin nano-drug can be simultaneously used for chemotherapy of leukemia and solid tumors, and has important practical significance.

The mechanisms driving the development of extracapillary lesions in focal segmental glomerulosclerosis (FSGS) and crescentic glomerulonephritis (CGN) remain poorly understood. A key question is how parietal epithelial cells (PECs) invade glomerular capillaries, thereby promoting injury and kidney failure. Here the inventors show that expression of the tetraspanin CD9 increases markedly in PECs in mouse models of CGN and FSGS, and in kidneys from individuals diagnosed with these diseases. Cd9 gene targeting in PECs prevents glomerular damage in CGN and FSGS mouse models. Mechanistically, CD9 deficiency prevents the oriented migration of PECs into the glomerular tuft and their acquisition of CD44 and β1 integrin expression. These findings highlight a critical role for de novo expression of CD9 as a common pathogenic switch driving the PEC phenotype in CGN and FSGS, while offering a potential therapeutic avenue to treat these conditions. Accordingly, CD9 represents a reliable biomarker and as well as a biotargets in glomerulonephritides.

The invention provides pharmaceutical compositions comprising human immature dental pulp stem cells (hIDPSCs) wherein the hIDPSCs express CD44 and CD13. The invention also provides methods of treating a neurological disease or condition comprising systemically administering to a subject a pharmaceutical composition comprising hIDPSCs wherein the hIDPSCs express CD44 and CD13. For example, for treating neurological diseases or conditions including supporting the neuro-protective mechanism in subjects diagnosed with early HD or repairing lost DA neurons in subjects diagnosed with PD.

The invention discloses a lipidosome composite hydrogel microsphere for repairing damaged intestinal mucosa and a preparation method thereof, LHMs (at) 4-OI is composed of hyaluronic acid modified targeted drug-loaded lipidosome, sodium alginate, hydrochloric acid treated sucralfate and a CaCl cross-linking agent, and rapid gel forming is carried out under the voltage of 11.0 KV through an electrospray technology. The microspheres have pH responsiveness and gastric juice digestion resistance, CD44 receptor targeting is achieved through hyaluronic acid modification, sodium alginate and Ca form an egg box structure to provide a three-dimensional network, and sucralfate enhances adhesion to isolate harmful substances. The preparation method comprises the steps of preparation of the drug-loaded liposome by a film hydration method, hyaluronic acid modification and electrospray crosslinking, is simple to operate and low in cost, and can be used for large-scale production. The microspheres can effectively load an anti-inflammatory drug 4-OI, inhibit expression of inflammatory factors and promote self-repair of damaged intestinal mucosa, and have wide application prospects in the fields of abdominal infection, inflammatory bowel diseases, colorectal cancer and the like.

The invention relates to an ROS-responsive macrophage-chondrocyte dual-targeting nano-micelle and a preparation method and application thereof, HA capable of targeting and highly expressing CD44 cells is taken as a carrier skeleton, chemical coupling with TK and CUR is carried out in sequence, self-assembly is carried out through intermolecular force to form a stable nano-micelle, and drugs JPH203 and KGN are entrapped at the same time, so that efficient loading and targeting delivery are realized. The HA can be specifically combined with RAW264.7 macrophages and articular cartilage cells for highly expressing a CD44 receptor in an inflammatory state, and is actively delivered in a targeting manner. The ROS response characteristic of TK is utilized, oxidative fracture is carried out in an OA high ROS microenvironment, and micelles are triggered to disintegrate and release drugs accurately. The released JPH203 can inhibit an inflammatory mTOR pathway and effectively resist inflammation, and KGN is beneficial to promoting cartilage cell proliferation and effectively collecting and promoting differentiation of mesenchymal stem cells into cartilage cells, so that in-situ cartilage regeneration is realized, and a more efficient solution with low side effects is provided for osteoarthritis treatment.

The application discloses a potential molecular marker for assisting in diagnosing cancer. The application provides application of a methylation CD44 gene as a marker in preparation of a product; the product is used for at least one of the following: assisting in diagnosing cancer or predicting a cancer morbidity risk; assisting in distinguishing a benign nodule and cancer; assisting in distinguishing different subtypes of cancer; assisting in distinguishing different stages of cancer; assisting in distinguishing different cancers; determining whether a to-be-tested substance hinders or promotes occurrence of cancer; and the cancer can be lung cancer or breast cancer. The application finds a low methylation phenomenon of the CD44 gene in blood of lung cancer and breast cancer patients, and has important scientific significance and clinical application value for improving early diagnosis and treatment effect of lung cancer and breast cancer and reducing mortality.

The invention relates to nanoparticles for enhancing the sonodynamic / chemical dynamic combined treatment effect by remodeling a tumor microenvironment, manganese metal is selected to be coordinated with a pyrrole ring of tetraphenylporphyrin, and manganese metalloporphyrin is endowed with the capabilities of consuming glutathione, realizing chemical dynamic treatment and enhancing the sonodynamic treatment effect. Meanwhile, the specific binding capacity of hyaluronic acid on tumor cell surface over-expressed CD44 receptors is utilized, cyclodextrin modified metal coordination tetraphenylporphyrin is delivered in a targeted mode, and accumulation of the sound-sensitive agent metalloporphyrin at the tumor site is increased. Based on host-guest interaction between beta-cyclodextrin and aminobenzimidazole, drug-loaded nanoparticles capable of responding to weak acid environment intelligent release are constructed. According to the nano-particle, the tumor microenvironment is remodeled to enhance the performance of inhibiting tumor growth through combination of sonodynamic force and chemical dynamic force, the raw materials are safe, non-toxic, low in cost and easy to obtain, and the nano-drug-loaded particle has the advantages of being easy to prepare, good in stability, high in biological safety and the like.

The invention relates to the technical field of biomedicine, in particular to a preparation method of sequential targeting mesoporous manganese oxide nano-enzyme and application of the sequential targeting mesoporous manganese oxide nano-enzyme in treatment of ischemia reperfusion induced acute kidney injury. Adding a potassium permanganate solution into the silicon dioxide nanoparticle dispersion liquid under ultrasonic waves, and carrying out alkali etching to obtain mesoporous manganese oxide nanoparticles (HMN); and after surface amination modification, connecting with a mixed PEG spacer layer, and reacting with thiolated SS31 and azidoacyl hyaluronic acid to obtain the nano-enzyme. The preparation can effectively penetrate through a damaged glomerulus filtration barrier and is passively enriched in a damaged kidney, damaged renal tubular epithelial cells over-express CD44 receptor mediated hyaluronic acid modified nano-particle endocytosis is enhanced, SS31 modified nano-particles achieve lysosome escape mitochondrial targeting in cells, the level of active oxygen in mitochondria can be reduced, and the activity of the mitochondria can be improved. The mitochondrial function is recovered, the renal function and tissue pathological injury are improved, and accurate anti-oxidation treatment on the acute kidney injury is realized.

The invention belongs to the technical field of biological medicines, and particularly discloses application of a CD44 function inhibitor in preparation of a medicine for preventing or relieving radiation liver injury (RILD). Radioactive liver injury is often caused by hepatocellular carcinoma radiotherapy, and specific targeting drugs are lacked clinically. It is revealed for the first time that whether CD44 molecules on the surface of Kuhu cells are highly expressed after radiation, and the CD44 molecules are key hubs for driving RILD; the invention also provides a CD44 function inhibitor which is a specific targeting drug aiming at RILD, and the action mechanism of the CD44 function inhibitor is to effectively block polarization of radiation-induced Kuptake cells to pro-inflammatory phenotype by inhibiting the CD44 function, so that local inflammatory response, oxidative stress and hepatocyte injury of the liver are relieved. Experiments prove that the CD44 function inhibitor can relieve liver inflammation, improve liver function indexes and reduce liver cell death and tissue pathological damage, and a brand-new and targeted scheme for preventing and treating RILD is provided.

The invention discloses a chondroitin sulfate modified dihydromyricetin solid lipid nanoparticle, and belongs to the field of pharmaceutics. The nanoparticle is composed of a solid lipid component, dihydromyricetin encapsulated in the solid lipid component and a chondroitin sulfate targeting ligand modified on the surface. According to the invention, the chondroitin sulfate is specifically combined with the high-expression CD44 receptor on the surface of the hepatic stellate cell, so that the active targeting delivery of the drug to the hepatic fibrosis focus is realized. The nanoparticles have the characteristics of uniform particle size, high encapsulation efficiency and good slow release effect, can significantly improve the enrichment concentration of dihydromyricetin in the liver, enhance the anti-hepatic fibrosis curative effect and reduce the systemic side effects, and have good application prospects in preparation of hepatic fibrosis targeted therapy drugs.

The invention discloses a method for detecting non-target cells in amniotic epithelial cells, which comprises reagents for detecting one or more of the following gene markers: FCGBP, RNASE6, DAB2, STAB1, RAB3IL1, CSF1R, CD68, CD209, EGFL7, LGALS2, LILRB4, HLA-DMB, HLADMA, CD74, ANPEP, CD44, CCR7, CD3G, CD3D, CD27, CD5, SPOCK2, TCF7, GZMH, KLRC2 and the like. Wherein the non-target cells are selected from macrophage-like cells, monocyte-like cells, T cell-like cells, NK cell-like cells, myeloid-like cells and neutrophil-like cells, a detection method is provided for quality control of the amniotic epithelial cells, and guidance is also provided for a cell product preparation process.

The invention discloses an application of a preparation for inhibiting the interaction of SPP1 / CD44 in preparing a medicine for preventing and / or treating nucleus pulposus cell degeneration, and relates to a method for effectively improving the nucleus pulposus cell function and degeneration by inhibiting the interaction of SPP1 / CD44 and inhibiting the nucleus pulposus cell degeneration induced by M1 macrophages. Potential intervention mechanisms and targets are provided for clinical prevention and treatment of the intervertebral disc degenerative diseases, and important research significance and clinical application prospects are achieved.

This invention discloses a dual-targeting biomimetic liposome composite material, its preparation method, and its application, belonging to the field of nanomedicine technology. Using liposome nanoparticles as a carrier, evolocumab and shikonin are loaded onto the carrier to obtain drug-loaded liposomes. These drug-loaded liposomes are then fused with macrophage membranes and modified with phospholipid-modified hyaluronic acid to obtain the dual-targeting biomimetic liposome composite material. This invention utilizes evolocumab for lipid-lowering effects and shikonin for anti-inflammatory effects, employing two different mechanisms to achieve targeted therapy for atherosclerosis. The outermost biomimetic membrane leverages the inherent immune escape and recruitment characteristics of macrophages to achieve long-term blood circulation and targeted ability to lesion sites. By utilizing the interaction between hyaluronic acid and the CD44 receptor on the target cell surface, the composite material is effectively utilized by target cells, enhancing its efficacy in preventing and treating atherosclerosis.

The invention discloses a cGAS-STING activated micro-needle system and a preparation method and application thereof.The cGAS-STING activated micro-needle system comprises a needle tip and a backing which are connected, the needle tip is loaded with a mesoporous photosensitive nano-composite drug, the mesoporous photosensitive nano-composite drug takes hollow Prussian blue nanoparticles as a carrier, the interior of the mesoporous photosensitive nano-composite drug is loaded with a small molecule drug, and the surface of the mesoporous photosensitive nano-composite drug is coated with a coating. The outer layer is coated with natural CD44 ligand polysaccharide; the small molecular medicine is a mixture of hydroxyurea and carotene. The mesoporous photosensitive nano-composite drug can induce death of immunogenic cells through mild photothermal induction, and release an injury-related molecular mode; meanwhile, a cGAS-STING signal channel is activated, secretion of type I interferon is promoted, and dendritic cells are induced to be activated and mature, so that T cell mediated anti-tumor immune response is enhanced. The invention provides an innovative tumor immunotherapy strategy and has important clinical application value.

To provide a preparation method and the use of a nanocarrier especially a liposome delivery system, in the diagnosis, prevention and treatment of a vulnerable plaque or a disease associated with the vulnerable plaque.SOLUTION: The present invention provides a liposomal nanocarrier delivery system for targeting an active CD44 molecule, preparation method therefor, and uses thereof. The surface of the liposome is partially modified by a targeting ligand, wherein the targeting ligand is a ligand that can be specifically combined with the active CD44 molecule. The liposomal nanocarrier delivery system can be used for diagnosing, preventing, and treating vulnerable plaque or diseases related to vulnerable plaque.SELECTED DRAWING: None

The invention discloses a diagnostic kit and a detection method for distinguishing human bone marrow from spleen neutrophil, and relates to the technical field of diagnostic kits and detection methods. The diagnostic kit comprises specific recognition components: a PE labeled monoclonal antibody clone DREG-56 aiming at a human CD62L antigen, an FITC labeled monoclonal antibody clone HA58 aiming at a human ICAM1 antigen, and an APC-Cy7 labeled monoclonal antibody clone G44-26 aiming at a human CD44 antigen. According to the invention, a new standard for identifying the source of neutrophil can be provided for clinic; the method can also be applied to hematopoietic system disease diagnosis, post-transplantation immune reconstruction monitoring and infectious disease progress evaluation, and has remarkable scientific research and industrialization popularization value.

The present disclosure relates to a TSG-6 fragment and a pharmaceutical composition for preventing or treating liver disease including the TSG-6 fragment as an active ingredient. The TSG-6 fragment according to the present disclosure inhibited the cleavage of CD44 by MMP-14 in human hepatic stellate cells, thereby inhibiting the expression of genes related to hepatic stellate cell activation and fibrosis. In addition, the TSG-6 fragment alleviated liver damage and inflammation in an alcohol-related liver disease mouse model and inhibited fatty liver and liver fibrosis. Therefore, the TSG-6 fragment according to the present disclosure may be used as various therapeutic agents for liver diseases accompanied by liver damage and liver fibrosis.

The invention provides a GSH (glutathione) reduction response type targeted nano-drug based on chondroitin sulfate as well as a preparation method and application of the GSH reduction response type targeted nano-drug. Chondroitin sulfate with CD44 receptor targeting ability and an anti-cancer drug camptothecin are covalently linked through a disulfide bond sensitive to GSH, and the constructed novel targeting nano-drug can accurately recognize human colorectal cancer tumor cells highly expressed by a CD44 receptor in a targeting manner. Meanwhile, the high-concentration glutathione at the tumor site can oxidize and reduce the disulfide bond to cause the fracture of AC-CPT NPs, so that the effective release of the camptothecin medicine at the tumor site is realized, and the anti-tumor effect is further enhanced. The reduction response type targeting nano-drug prepared by the invention solves the problems of poor targeting and biological solubility and limited treatment effect of the traditional anti-cancer drug camptothecin, and provides an innovative strategy for realizing accurate targeting and efficient treatment of cancers.

The invention discloses a nano blocker for hyaluronic acid energy metabolism of a targeted CD44 receptor as well as a preparation method and application of the nano blocker. The nano blocker is a nano preparation obtained by modifying a polylactic acid-glycolic acid copolymer (PLGA) with hyaluronic acid (HA) and then coating the PLGA with nebivolol hydrochloride and 3-bromopyruvic acid, and the nano preparation is marked as NBP-coated PLGA-HA. According to the CD44 receptor targeted hyaluronic acid energy metabolism nano blocking agent disclosed by the invention, bidirectional blocking of basic respiration of tumor cells is realized by using a loaded mitochondrial oxidative phosphorylation (OXPHOS) inhibitor nebivolol hydrochloride and a glycolysis inhibitor 3-bromopyruvic acid; meanwhile, effector immune cells are synergistically enhanced to maintain systemic anti-tumor immunity, high efficiency and safety are shown in in-vitro and in-vivo experiments, and concept paradigm transformation is provided for nano-drug mediated tumor treatment based on energy metabolism.

The invention discloses a 15-antibody combination for accurately detecting a mouse tissue immune cell subset and application of the 15-antibody combination. Aiming at the problems of large fluctuation and instability of detection results caused by adjustment of voltage and fluorescence compensation during detection by a flow cytometer and different processing modes during result analysis, the antibody combination disclosed by the invention takes monoclonal antibodies CD45, CD3, CD4, CD8, CD19, B220, Ly-6C, Ly-6G, MHC-II, CD11c, CD49b, CD62L, CD44 +, PD-1 and PD-L1 as effective components, and a stable and standard detection method for mouse tissue immune cell subsets is established. The method can analyze the proportion, number and distribution of various immune cells (T cells, B cells, NK cells, dendritic cells, mononuclear cells and granulocytes) in spleen, lung, liver, brain or kidney tissues of mice, can reflect the immune state of the mice and evaluate the immunosuppression state, and can be applied to the fields of disease models, drug evaluation, vaccine development and the like.