210 results about "CD44" patented technology

The invention relates to protein nanoparticles for treating ulcerative colitis as well as a preparation method and application thereof, and relates to the field of nano pharmaceutical preparations. 5-aminosalicylic acid is encapsulated in zein to achieve the purpose of improving the bioavailability of the 5-aminosalicylic acid by preparing protein nanoparticles of a targeted inflammation colon part, mannose grafted hyaluronic acid is used as a stabilizer to be attached to the surfaces of the zein nanoparticles through electrostatic adsorption and hydrogen-bond interaction, and the bioavailability of the 5-aminosalicylic acid is improved. Mannose can be targeted to immune cells through a mannose receptor, and can be cooperated with 5-aminosalicylic acid to treat ulcerative colitis. The hyaluronic acid has the effects of stabilizing the protein nanoparticles and targeting macrophages and intestinal epithelial cell CD44 receptors in ulcerative colitis tissues, so that aggregation of the nanoparticles in the colitis tissues is mediated, the protein nanoparticles have the functions of resisting inflammation, resisting oxidation and repairing barrier injury, and a new research direction is provided for treatment of ulcerative colitis.

The invention relates to a pathologically responsive nano-carrier as well as a preparation method and application thereof, belongs to the technical field of biological medicines, and aims to solve the problems that in the prior art, nano-particles are enriched in livers and kidneys in quantity, the risk of damaging organs and tissues exists, toxic and side effects on patients with spinal cord injury are large, the treatment effect is not obvious and the like. The carrier is a self-assembled nanoparticle which takes PLGA as a skeleton structure, is externally modified with hyaluronic acid and is connected with RVG29 through a diselenide bond. The carrier can load an active substance, such as curcumin, can be used for treating spinal cord injury, and can target spinal cord tissues through intravenous administration, penetrate a blood spinal cord barrier, target CD44 through HA at the early stage of injury, increase immune cell uptake and inhibit inflammatory infiltration and inflammatory cascade. In the late stage of injury, the nerve cell uptake is increased through RVG29 targeted acetylcholine receptor (nAchR), and nerve repair and regeneration are promoted.

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 targeting exosome preparation, and particularly relates to a targeting modification method of a rose exosome, a hyaluronic acid modified rose exosome and application of the hyaluronic acid modified rose exosome. The method comprises the following steps: dissolving hyaluronic acid in a rose exosome, adding 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and N-hydroxysuccinimide, carrying out a reaction for 8-16 h, carrying out centrifugation, and carrying out resuspension precipitation so as to obtain a hyaluronic acid modified rose exosome; the volume mass ratio of the hyaluronic acid to the rose exosome solution is 1 mg: (0.5-1) ml, and the hyaluronic acid, the 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide and the N-hydroxysuccinimide are in an equal molar ratio. The characteristic that hyaluronic acid is highly compatible with an inflammatory cell CD44 receptor is utilized, the targeting property of the rose exosome to inflammatory cells is enhanced, and the utilization rate and the anti-inflammatory effect of the rose exosome are further improved.

The invention discloses a natural product-based nano antioxidant for treating acute pancreatitis and a preparation method of the natural product-based nano antioxidant, and relates to the technical field of biological medicines. 25 mg of ferulic acid (FA); and 15 mL of 80% (v / v) ethanol-deionized water solution. According to the natural product-based nano antioxidant for treating acute pancreatitis and the preparation method thereof, the nano antioxidant effectively targets inflammatory pancreatic tissues through the specific interaction of chondroitin sulfate (CS) and CD44, and is split and released under the stimulation of pH / GSH and H2O2 in cells to generate FA and zein degradation products, the FA and zein degradation products efficiently play a synergistic role in removing ROS, and the natural product-based nano antioxidant can be used for treating acute pancreatitis. Therefore, inflammation is relieved; the nano antioxidant shows an excellent in-vivo treatment effect on acute pancreatitis and has a clinical application prospect.

The invention discloses a dual-targeting bionic liposome composite material and a preparation method and application thereof, and belongs to the technical field of nano-medices.The dual-targeting bionic liposome composite material is prepared by taking liposome nano-particles as a carrier, loading iloumab and alkannin on the carrier to obtain drug-loaded liposome, and fusing the drug-loaded liposome with a macrophage membrane to obtain the dual-targeting bionic liposome composite material. And modifying with phospholipidic hyaluronic acid to obtain the double-targeting bionic liposome composite material. According to the invention, two anti-atherosclerosis effects with different mechanisms, i.e., lipid lowering by Elolukumab and anti-inflammation by alkannin, are utilized to realize targeted therapy of atherosclerosis, and the bionic membrane on the outermost layer realizes long blood circulation and lesion site targeting ability of the composite material through inherent immune escape and recruitment characteristics of macrophages. The characteristic that hyaluronic acid interacts with a target cell surface receptor CD44 is utilized, effective utilization of the target cell on the composite material is achieved, and the atherosclerosis prevention and treatment effect of the composite material is improved.

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 CD44-mediated self-assembled nanoparticles as well as a preparation method and application thereof, and belongs to the technical field of biology. The CD44-mediated self-assembled nanoparticles are formed by self-assembling polylysine with a phenylboronic acid side chain and dopamine-modified hyaluronic acid through electrostatic interaction, and the side-chain phenylboronic acid of the polylysine is connected with the side-chain dopamine on the hyaluronic acid through a covalent bond. The surface of the nanoparticle is connected with a target protein binding unit through a linker, and the target protein binding unit is used for binding a target protein. The synthesis process is simple, the components are safe, the prepared CD44-mediated self-assembled nano material can efficiently degrade tumor cell extracellular proteins such as PD-L1 and HER2, the specificity is high, the degradation rate is high, and the CD44-mediated self-assembled nano material has a very good application prospect in the field of treatment of diseases such as tumors.

The invention relates to a CD44 receptor and scavenger receptor-A (SR-A) dual-targeting pharmaceutical composition as well as a preparation method and application thereof. According to the invention, a certain proportion of carrier material with CD44 receptor targeting capability is adsorbed on the fatty acid albumin nanoparticles, and the albumin nanoparticles with CD44 receptor and SR-A dual-targeting capability are successfully prepared. The albumin nanoparticles can simultaneously deliver drugs to activated macrophages with high SR-A specificity expression and fibroblasts or tumor cells with high CD44 receptor specificity expression, provide new treatment schemes and ideas for various diseases including tissue fibrosis and tumors, and have great application value in the field of biological medicine.

The invention relates to the field of bioengineering, in particular to a preparation method of cells and application of the cells in cell effectiveness detection. The invention provides a cell culture method which comprises the following steps: carrying out first stimulation, first culture, second stimulation, blocking, second culture and cleaning on pretreated cells to obtain the cells. The invention provides a method for determining the effectiveness of an immune cell preparation activated in vitro, according to the characteristics of the immune cell preparation activated in vitro, a two-step stimulation activation mode is adopted, the activation ratio of CD69 + CD44 + is used as a systematic internal control index of the method, and meanwhile, the mechanism of the immune cell preparation activated in vitro is combined to determine the effectiveness of the immune cell preparation activated in vitro. The Tc cell subpopulation secreting granzyme B is used as a method detection index, so that the indirect evaluation of the effectiveness of the immune cell preparation activated in vitro in human body is realized, and the method can be used for release detection of the immune cell preparation activated in vitro in human body.

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 embodiment of the invention discloses a teprenone-containing composition, a skin care product and application. The teprenone-containing composition and the skin care product can promote the expression of CD44. The composition containing the teprenone is prepared from the teprenone and acetyl tripeptide-30 citrulline, and the mass ratio of the teprenone to the acetyl tripeptide-30 citrulline is 50 to (15 to 25).

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.

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.

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 present disclosure provides a tumor-targeting composite nanozyme material, a preparation method thereof, and an application thereof. A copper ion-doped metal-organic framework material UiO66-NH2(Cu) is in-situ grown on the surface of magnetic nanoparticles to form a core-shell structure, and then oxidized hyaluronic acid is bonded to the surface of the core-shell structure, and then a chemotherapeutic drug is loaded to obtain the tumor-targeting composite nanozyme material. The present invention utilizes the magnetism of the magnetic nanoparticles to exert targeting through physical action and enrich the nanoparticles at the tumor site. Further, by modifying the surface of the nanoparticles with oxidized hyaluronic acid, the nanoparticles conjugated with oxidized hyaluronic acid are transported into tumor cells under the mediation of CD44 molecules, realizing precise drug release with dual targeting. In addition, the composite nanozyme catalyzes H2O2 into toxic ·OH to cause apoptosis of tumor cells, consumes GSH, inhibits the in vivo antioxidant system, reduces the consumption of ROS, and generates a cascade amplification enzymatic reaction through the cycle of multivalent metal ions, achieving the maximum killing effect on 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 invention discloses novel cascaded targeted selenium-based hydrogel microspheres for multi-stage antioxidant treatment of osteoarthritis and a preparation method of the novel cascaded targeted selenium-based hydrogel microspheres. The preparation method comprises the following steps: step S1, preparing an LAP solution; s2, preparing a hydrogel precursor solution; s3, preparing a hydrogel oil phase for later use; step S4, preparing hydrogel microspheres with a porous structure; and step S5, preparing the hydrogel microspheres (AHAMA-HMs) loaded with the novel selenium nanoparticles (HA-SeNPs). The AHAMA hydrogel microspheres loaded with the HA-SeNPs can enter an articular cavity through a 5mL injector, and the cartilage is adhered and abraded in a targeted manner by virtue of a Schiff base reaction of-CHO on the surface of the microspheres and-NH2 on the surface of the cartilage, so that micron-level targeting is realized; then, HA-SeNPs released from the AHAMA-HMs is combined with CD44 on the surface of the abraded cartilage cell through hyaluronic acid (HA), so that nano-scale targeting is realized. Subsequently, after entering the cartilage cells, the HA-SeNPs can participate in removal of excess reactive oxygen species (ROS) in the cells in multiple stages, so that multi-stage antioxidant treatment is realized, and further osteoarthritis is treated.

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 the technical field of drugs, in particular to multifunctional polymyxin B nanoparticles and preparation and application thereof.The multifunctional nanospheres (HPK) of polymyxin B (PMB) are synthesized by connecting hyaluronic acid and polymyxin B through Schiff base bonds and combining KAFAK, and the multifunctional nanospheres (HPK) serve as candidate drugs for refractory infectious diseases and can release PMB in response to the infected microenvironment, so that the effect of treating the refractory infectious diseases is achieved. The targeted infection site removes bacteria and various inflammatory mediators to reduce cytokine storm, including removal of LPS and active oxygen, and inhibition of macrophage activation. Hyaluronic acid (HA) serves as a carrier of PMB, the HA and the PMB are tightly connected through a pH sensitive bond Schiff base bond, the hyaluronic acid can change the biological distribution condition of the PMB, and a targeted CD44 receptor, hyaluronidase and the Schiff base bond can achieve PMB acidic microenvironment targeted delivery and meanwhile cooperate with PMB to resist bacteria and KAFAK to resist inflammation. The design and preparation of HPK effectively achieve the effects of reducing toxicity and enhancing efficacy on PMB.

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.