24 results about "Tumor penetration" patented technology

The invention discloses a conical asymmetric nano robot for deep tumor penetration as well as a preparation method and application of the conical asymmetric nano robot. The structure of the asymmetric nano robot is Fe3O4 (at) mPDA (at) MnO2amp; mSiO2, and is marked as FPMamp; s; an FPMamp (Fabry Perot Module); the S nano-robot is nano-particles of an asymmetric structure, one end of the asymmetric structure is of a core-shell structure, the core is spherical Fe3O4, and the shell is mesoporous polydopamine particles; one end of the rod-like structure, which is far away from the Fe3O4, is conical; mnO2 is loaded on the surface of the mesoporous polydopamine; the asymmetric structure with the conical tail part is constructed, so that the forward wedging capability of the nano-robot in the moving process is improved, and the deep tumor penetrating performance is fundamentally improved; through the same nanorobot, collaborative treatment of multiple mechanisms of photo-thermal-Fenton-GSH depletion in space and time is achieved, the overall treatment efficiency of a deep tumor area is improved, and the problems that an existing asymmetric micro / nanorobot is insufficient in deep tumor penetrating capacity, the collaborative efficiency of a treatment module is limited and the like are solved.

The invention provides an application of M1 as an affinity of human source PD-L1 and / or mouse source PD-L1, and relates to the technical field of biological medicine. The invention proves that M1 can be used as a PD-L1 affinity for human / mouse cross reaction, and has low nanomole affinity for two targets. In cell-based function detection, M1 has similar affinity with mPDL1 and hPD-L1 expressed on the surface of a cell, and signal transduction is inhibited through a PD-L1: PD1 axis at a low micromolar concentration. The M1 disclosed by the invention can be used as a non-antibody treatment method to damage a PD-L1: PD1 signal channel, and the M1 shows high tumor permeability compared with an antibody, and particularly has a remarkable advantage in tumors (such as pancreatic tumors) with high fiber hyperplasia; the M1 shows selective uptake in the tumor for expressing the PD-L1.

The application relates to a carrier-free self-driven nanomotor and a preparation method and application thereof, and belongs to the technical field of biological medicines. The nanomotor is a nanometer assembly formed by co-assembly of a photothermal / light motion dual-enhanced photosensitizer and a near-infrared light response type nitric oxide donor BNN6 through intermolecular force, or is a nanometer assembly formed by co-assembly of a photothermal / light motion dual-enhanced photosensitizer and a near-infrared light response type nitric oxide donor BNN6 through intermolecular force and modified by a polyethylene glycol modifier. The application realizes a synergistic treatment mode of deep tumor penetration and high-efficiency killing by constructing a functional coupling system of "photothermal driving-NO release-motion enhancement-RNS cascade generation".

The application discloses a tumor-penetrating carrier-free nanomedicine as well as a preparation method and application thereof, and belongs to the field of nanomedicine. The carrier-free nanomedicine can significantly improve water solubility of a water-insoluble compound, has mitochondrion targeting and tumor active penetration capabilities, and under the action of a tertiary amine nitrogen oxygen group, the carrier-free nanomedicine can be mostly transported into mitochondria, which is beneficial to inducing a mitochondrion membrane potential drop and cell apoptosis. The carrier-free nanomedicine also has a good blood long-circulation effect and tumor accumulation capability in a body, and an antitumor effect is better than that of a clinical drug, and the carrier-free nanomedicine also has good biological safety. The preparation method is simple, and can be used for preparation of an antitumor drug.

This invention relates to biomimetic mineralized exosomes for programmed drug penetration in tumors that inhibit cell burial, along with their preparation method and applications. Belonging to the field of novel excipients and dosage forms for pharmaceutical formulations, this invention co-loads the small-molecule chemotherapeutic drugs 10-hydroxycamptothecin and banoanthraquinone into exosomes. Then, through a biomimetic mineralization strategy, aTIM-4 is organically combined with mineralized calcium phosphate particles to obtain biomimetic mineralized exosomes. Under the acidic response of the tumor microenvironment, the calcium phosphate shell dissolves, and the exosome nucleus enters the tumor cells, inducing cell death and generating apoptotic bodies. This programmatically delivers the drug, delivering banoanthraquinone deep into the tumor. Simultaneously, the released aTIM-4 inhibits the cell burial of tumor-associated macrophages, amplifying the programmed drug penetration based on apoptotic bodies. This invention provides a new strategy and more options for overcoming the bottleneck of nanomedicine penetration in tumors, meeting the urgent clinical need for highly effective chemotherapeutic agents.

This invention provides a CD24-targeted nanomedicine delivery system and its application in the preparation of antitumor drugs. The nanomedicine delivery system of this invention comprises (1) a core structure: mesoporous manganese dioxide (hMnO₂) for co-loading glucose oxidase (GOx) and cysteine ​​(Cys); and (2) targeted delivery: nanoparticles encapsulated in a genetically engineered membrane EM-CD24 modified with the anti-CD24 single-chain variable fragment scFv. This invention can improve tumor penetration, reduce off-target accumulation, and enhance pharmacokinetics, achieving therapeutic Gox and cysteine ​​concentrations in the tumor while maintaining low systemic exposure, thus minimizing off-target toxicity.

The invention belongs to the technical field of biological medicine, and particularly relates to a nanometer drug delivery system with a tumor deep penetration effect and a preparation method and application of the nanometer drug delivery system. The polylactic acid-glycolic acid nano-particles are polylactic acid-glycolic acid copolymer nano-particles entrapped with chemotherapeutic drugs and carbon monoxide donors; the chemotherapeutic drug is monomethyl aurestatin E, and the carbon monoxide donor is S-nitroso-N-acetyl-DL-penicillamine; a lipid layer; the core is coated with the core; the targeting polypeptide is modified on the surface of the lipid layer; the targeting polypeptide is an R4F polypeptide; tumor cells are actively targeted through R4F polypeptide, the polylactic acid-glycolic acid copolymer nanoparticles wrapped by a lipid layer deeply penetrate into tumor tissues, nitric oxide is released through a carbon monoxide donor to degrade an extracellular matrix barrier, and deep penetration of loaded chemotherapeutic drugs and immune cells in the tumor tissues is synergistically promoted; the nano drug delivery system provided by the invention can be applied to preparation of drugs for treating solid tumors and delivery of drugs for targeting extracellular matrixes of the solid tumors.

The invention discloses a bionic photo-thermal nano motor for targeted regulation and control of a solid tumor matrix-immunosuppression microenvironment and a preparation method and application thereof, and belongs to the technical field of biomedical materials.The preparation method comprises the steps that polydopamine nanoparticles and a K2PtCl4 aqueous solution are subjected to condensation reflux, and asymmetric PDA-Pt is prepared; and preparing a cancer-related fibroblast and breast cancer cell fusion membrane and coating the surface of PDA-Pt with the cancer-related fibroblast and breast cancer cell fusion membrane. The nano-motor realizes dual targeting of matrix cells and tumor cells through a surface modified fusion cell membrane, targeted ablation CAFs regulates and controls a tumor matrix microenvironment, a good tumor permeation effect is realized by cooperating with H2O2 responsive self-driving of the nano-motor, a mild photo-thermal-catalytic synergistic effect is formed by a photo-thermal effect of PDA and peroxidase-like activity of Pt nano-enzyme, and a good tumor permeation effect is achieved. And finally, the tumor immunosuppression microenvironment is remarkably improved, and the tumor immunotherapy effect is improved.

The invention discloses a tumor cell-derived drug-loaded vesicle and temperature-sensitive nanogel composition and a preparation method and application thereof, and belongs to the technical field of tumor treatment, and the composition comprises a poly-N-isopropylacrylamide-butyl methacrylate nanogel, iohexol and a drug-loaded vesicle. According to the tumor cell-derived drug-loaded vesicle and temperature-sensitive nanogel composition as well as the preparation method and the application thereof, the bioavailability of Dug (at) MPs is improved, the bioavailability of non-target visceral organs is reduced, the intra-tumor penetration distance of the drug is increased, precise cooperation of chemotherapy and interventional embolism treatment is realized, and the curative effect of the drug is improved. The medicine is far better than interventional embolism therapy or conventional interventional embolism chemotherapy, and recurrence and metastasis of tumors are effectively inhibited.

The invention discloses an intelligent transdermal drug delivery system based on a tripterygium wilfordii exosome and a ferroptosis inducer as well as a preparation method and application of the intelligent transdermal drug delivery system, and belongs to the technical field of biological medicines. The method comprises the following steps: extracting tripterygium wilfordii exosomes (TExos) with natural anti-tumor activity, fusing the tripterygium wilfordii exosomes with a homologous tumor cell membrane by utilizing a repeated freeze-thaw method to construct a bionic targeting compound (CTE), and then loading RSL3 through a co-incubation method to form an R (at) CTE compound. The compound is further loaded into a porous microneedle through a 3D printing technology to prepare an R-(at) CTE-M transdermal drug delivery system. The drug delivery system constructed by the invention has excellent homologous targeting property and tumor penetrating ability, can effectively inhibit proliferation, migration and invasion of triple negative breast cancer cells, induce cell apoptosis and enhance cell ferroptosis, and shows a remarkable tumor inhibition effect and good biological safety in an animal model.

PSMA targeted metal chelate nanodrugs, methods of making these nanodrugs and methods of using them for radiodiagnosis and radiotherapy are provided.

This invention discloses a method for preparing and applying a chimeric peptide nanomedicine for photodynamic immunotherapy of triple-negative breast cancer. The nanomedicine uses the functional chimeric peptide Fmoc-K(PpIX)-PLGLAG-CVRARTR as its self-assembly core and is loaded with the exosomal PD-L1 inhibitor GW4869. This chimeric peptide contains an MMP-2 responsive sequence, the photosensitizer PpIX, and the PD-L1 targeting peptide CVRARTR. It is structurally stable in the bloodstream and can specifically accumulate in tumor tissues that highly express PD-L1 via the targeting peptide. Enzymatic degradation is triggered by the highly expressed MMP-2 in the tumor microenvironment, achieving structural deformation, controlled drug release, and enhanced deep tumor penetration. This invention can simultaneously achieve a triple synergistic therapeutic effect: PDT generates reactive oxygen species that directly kill tumor cells and trigger immunogenic cell death, enhancing immunogenicity; the targeting peptide competitively blocks PD-L1 on the cell surface, relieving local immunosuppression; and the inhibitor downregulates exosomal PD-L1 secretion, inhibiting systemic immune escape. This approach effectively overcomes the bottleneck of low response rates in existing TNBC immunotherapy.

The application provides a tumor microenvironment acid response deep penetration nanogel and application thereof. Specifically disclosed is an acid response nanogel carrier, wherein the nanogel carrier is obtained by polymerization of double-bonded hyaluronic acid, double-bonded cyclodextrin and 2,2-dimethyl acryloyl oxy-1-ethoxy propane under the action of a free radical polymerization initiator; the double-bonded hyaluronic acid is obtained by modification of hyaluronic acid with an acrylic anhydride compound; and the double-bonded cyclodextrin is obtained by modification of a cyclodextrin compound with an olefin acyl chloride compound. Further disclosed is an acid response nanogel loaded with an active ingredient, wherein the acid response nanogel carrier is used as an active ingredient carrier, and the active ingredient is included in the double-bonded cyclodextrin. The nanogel prepared by the application has good acid response performance and drug loading capacity, and has excellent tumor penetration capacity, which is beneficial to enhancing the anti-tumor effect of the drug or for detection.

The invention discloses a nano-engineered mononuclear cell and application thereof, and belongs to the technical field of medicines. The nano-engineered mononuclear cell comprises a mononuclear cell, a nano-engineered element and a therapeutic drug, the nano-engineered element is loaded in cytoplasm of the mononuclear cell, and the surface of the mononuclear cell is modified with the therapeutic drug; the nano engineered element is iron oxide nanoparticles; the therapeutic drug is a functional lipid obtained by modifying a chemotherapeutic drug on a lipid molecule. The nano-engineered mononuclear cell can retain and even enhance the tumor tropism and tumor infiltration capacity of the mononuclear cell, can effectively intervene in the differentiation phenotype of the mononuclear cell in vivo and in vitro, relieves the tumor immunosuppression microenvironment, inhibits the growth of tumor cells, and achieves a good anti-tumor effect.

The present application relates to the technical field of medicine, and relates to an engineered exosome ball delivery system loaded with a therapeutic drug and a preparation method and application thereof. The system is a platelet exosome loaded with a therapeutic drug, and then the surface phosphatidylserine of the drug-loaded exosome is shielded, that is, the exosome ball delivery system is obtained. Compared with the exosome, the exosome ball has stronger resistance to macrophage phagocytosis, longer blood circulation time, and better tumor penetration ability than the platelet. In addition, among the tested preparations, the exosome ball shows higher uptake rate of tumor cells and produces the strongest tumor inhibition effect, and can well inhibit tumor growth and eliminate circulating tumor cells. These findings show that the exosome ball solves the limitations of the biological carrier system and provides great potential for efficient and precise drug delivery.

The invention discloses a self-assembly aggregation-induced emission nanoprobe for targeted therapy and real-time imaging of non-small cell lung cancer and application, and belongs to the technical field of biological medicine. According to the invention, a self-assembled AIE compound with a structure of TPE-FFNPGYGKSLSRHDHIHHHPLGVR-PEG6 is firstly synthesized, the self-assembled AIE compound is self-assembled to form a self-assembled aggregation-induced emission nano-probe AIInps for targeting c-Met, and the AIInps has dual functions of realizing real-time imaging through fluorescence tracking, realizing targeted therapy by inhibiting the c-Met, realizing tumor specific accumulation and fluorescence tracking based on the design of the AIE, and realizing targeted treatment by inhibiting the c-Met. The AInps is a multifunctional NSCLC treatment platform, integrates targeted treatment and real-time imaging and has a very wide application prospect, and the limitation of poor tumor permeability and non-specific distribution in a traditional therapy method is overcome by the aid of the AInps, and the AInps is a multifunctional NSCLC treatment platform and integrates targeted treatment and real-time imaging.

The application discloses a self-assembled aggregation-induced emission nanoprobes for targeted therapy and real-time imaging of non-small cell lung cancer and application, and belongs to the technical field of biological medicine. The self-assembled aggregation-induced emission nanoprobes AIEnps are used for targeting c-Met, and the AIEnps have a dual function: one is to realize real-time imaging through fluorescence tracing, and the other is to realize targeted therapy by inhibiting c-Met. The design based on AIE realizes tumor-specific accumulation and fluorescence tracing, overcomes the limitations of poor tumor permeability and non-specific distribution in traditional therapy, and the AIEnps are a multifunctional NSCLC treatment platform, integrating targeted therapy and real-time imaging, and have a very broad application prospect.

This invention discloses a metal nanoparticle hybrid polymeric vesicle, its preparation method, and its applications. The method includes the following steps: adding a block copolymer solution to a metal salt aqueous solution via a syringe pump, i.e., preparing a preliminary hybrid vesicle by solvent exchange; dialyzing the obtained preliminary hybrid vesicle to remove unloaded metal ions; and adding an oxidizing agent or a reducing agent to the dialyzed preliminary hybrid vesicle to obtain the metal nanoparticle hybrid polymeric vesicle. This invention is simple to operate and highly reproducible. The prepared hybrid polymeric vesicle can act as a nanomotor during drug delivery, increasing tumor penetration under the driving force. After intracellular degradation, the metal nanoparticles can also act as nanozymes to produce therapeutic effects. This hybrid polymeric vesicle has excellent drug delivery capabilities and nanozyme characteristics, showing promising applications in drug delivery systems and the preparation of tumor therapeutic drugs.

Provided is use of annexin in improving the tumor penetration efficiency of a nanocarrier with a phospholipid surface. The present invention innovatively explored a protein capable of promoting the tumor penetration efficiency of a phospholipid-based nanocarrier, and found that coating the phospholipid-based nanocarrier with annexin can improve the tumor penetration efficiency, thereby improving the bioavailability of a drug loaded with the nanocarrier and improving the therapeutic effect. In addition, it is also found that the efficiency-enhancing ability of annexin is positively correlated with the expression level of integrin α5 or β1. By means of pre-detecting and analyzing the expression level of integrin α5 or β1 in a patient, the ability of annexin coating technology to promote the transport of nanocarriers can be predicted, and the beneficiary population suitable for the use of the annexin coating technology can be screened.

The invention relates to a nano-drug based on a collagenase infiltration strategy and application of the nano-drug in deep tumor chemotherapy-immune collaborative therapy. Aiming at the problems of insufficient permeation, low accumulation rate and large toxic and side effects of traditional chemotherapeutic drugs caused by a shielding effect of a tumor tissue microenvironment on the nano-drugs, bovine serum albumin is used as a carrier, collagenase and low-dose docetaxel are co-entrapped through a self-assembly method, and a nano-particle drug (COL / DTX-coated BSA NPs) is constructed. The nano-drug has the characteristics of uniform spherical morphology, high encapsulation efficiency and drug loading capacity, good collagenase activity maintenance, excellent biocompatibility and the like, and collagenase-mediated tumor penetration enhancement, a low-dose chemotherapy-immune synergistic mechanism and safety guarantee can be realized. Tumor targeted enrichment and deep penetration are realized in a breast cancer model, chemotherapy tumor inhibition effect and anti-tumor immunity are synergistically enhanced, system toxicity is remarkably reduced, and a new strategy is provided for high-efficiency and low-toxicity treatment of solid tumors.

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

This invention belongs to the field of novel excipients and dosage forms for pharmaceutical preparations, specifically relating to a core-shell structured sequential drug delivery system for cascaded deep penetration and differentiation-inducing therapy, its construction, and its application in drug delivery systems. The system has a core-shell structure, with the core consisting of hypoxia-responsive nanoparticles encapsulating differentiation-inducing agents, and the shell being an acid-responsive reversible polymer loaded with chemotherapeutic drugs. This invention overcomes the penetration barrier of solid tumors using a pulsed drug delivery strategy and performs programmed drug delivery targeting the heterogeneous distribution of different cells within the tumor, effectively reshaping the tumor microenvironment characterized by chemotherapy resistance and immune escape, thus achieving comprehensive tumor inhibition.

The invention provides a CD24-targeted nano-drug delivery system and an application of the CD24-targeted nano-drug delivery system in preparation of anti-tumor drugs. The nano-drug delivery system comprises (1) a core structure: mesoporous manganese dioxide hMnO is used for co-loading glucose oxidase GOx and cystine Cys; and (2) targeted delivery: coating the nanoparticles with a gene engineering membrane EM-CD24 modified by an anti-CD24 single-chain variable fragment scFv. According to the invention, tumor penetration can be improved, off-target accumulation can be reduced, and pharmacokinetics can be enhanced, so that low systematic exposure can be maintained, therapeutic Gox and cystine concentrations in tumors can be achieved, and off-target toxicity can be reduced to the greatest extent.

This invention relates to Furin / hydroxyl radical dual-responsive size-changing nanoparticles, their preparation, and applications. The Furin / hydroxyl radical dual-responsive size-changing nanoparticles use an AIE photosensitizer as the core and DSPE-PEG as the substrate. 2K MAL nanoparticles serve as carriers, with functional peptides coupled to their surfaces via Michael addition reactions. The core functional building block is a self-designed and custom-synthesized R1 peptide, which possesses a triple function: high specificity recognition by Furin protease, OH-responsive tyrosine oxidation cross-linking, and coupling with DSPE-PEG nanoparticles. Its simple sequence significantly enhances tumor selectivity. The peptide is covalently modified with natural peptides using a nanoprecipitation method, avoiding complex chemical modifications and exogenous orthogonal biological groups, thus mitigating the toxicity and synthesis costs of traditional systems. Under the dual conditions of Furin protease overexpression and the presence of OH, size transformation is triggered, enabling deep tumor penetration with small sizes and long-term intratumoral retention through in-situ large-size assembly, demonstrating clinical translational potential.