WO2023113550A1 - Nanostructure fonctionnelle imitant une cellule dendritique, et son procédé de production - Google Patents

Nanostructure fonctionnelle imitant une cellule dendritique, et son procédé de production Download PDF

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WO2023113550A1
WO2023113550A1 PCT/KR2022/020615 KR2022020615W WO2023113550A1 WO 2023113550 A1 WO2023113550 A1 WO 2023113550A1 KR 2022020615 W KR2022020615 W KR 2022020615W WO 2023113550 A1 WO2023113550 A1 WO 2023113550A1
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cell
dendritic cell
spherical core
dendritic
nanoparticles
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Korean (ko)
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하상준
문채원
김다혜
홍진기
김태현
이유진
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주식회사 포투가바이오
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5123—Organic compounds, e.g. fats, sugars
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5176—Compounds of unknown constitution, e.g. material from plants or animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5192—Processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders

Definitions

  • the present invention relates to a dendritic cell-mimicking functional nanostructure and a method for preparing the same.
  • Cancer is the number one cause of death in Korea.
  • Representative cancer treatment methods may include surgical operation to remove cancer, radiation treatment, and chemical drug treatment, but these treatment methods have a problem in that they have a poor prognosis and serious side effects.
  • the main cause of cancer is formation of tumors by cancer cells that have not been removed according to the immune response due to reduced immunity or immune evasion of cancer cells. Therefore, immuno-anticancer therapy that can help cancer treatment by increasing the patient's own immune response can be a fundamental cancer treatment.
  • Most of the currently developed immuno-anticancer treatments directly inject drugs that enhance immune function, but drug injection still has limitations in that the delivery efficiency is very low and additional side effects may exist. Accordingly, research is focused on the development of therapeutic agents capable of dramatically increasing cancer treatment efficiency, reducing recurrence rates and side effects, and enhancing immune function.
  • the nanoparticle-cellularization technology uses the entire cell membrane of a specific cell as a coating material to physically cloak the surface of the nanoparticle. It can maintain the complex properties of the cell membrane along with proteins, lipids, and carbohydrates, and thus the surface of the nanoparticle.
  • the characteristics of a specific cell can be implemented as it is.
  • Non-Patent Document 0001 Hu, Che-Ming J., et al. Nature, 2015, 526(7571) 118-12
  • Non-Patent Document 0002 Brian T. Luk et al., Theranostics. 2016, 6(7), 1004-1101
  • Non-Patent Document 0003 Q. Jiang et al., Biomaterials 2019, 192, 292-308
  • the present disclosure seeks to more effectively implement the cancer treatment effect according to the increase in the immune response by using cells having an antigen presenting function beyond the material limitations of the prior art. Specifically, through a structure that mimics dendritic cells, cytotoxic T cells are directly activated according to the antigen presenting function of dendritic cells in the body, inducing selective death of cancer cells, and providing excellent immunotherapy effects by increasing the immune response. is to do
  • an object of the present disclosure is to impart functionality through the design of nanostructures to realize more marked activation of cytotoxic T cells and to provide more enhanced immunotherapeutic effects.
  • Dendritic cell-mimicking structure in order to achieve the above object is non-spherical core particles; And a shell comprising a cell membrane of lipid molecules derived from dendritic cells; the shell may be characterized in that it comprises a bilayer of the lipid molecules.
  • the non-spherical core particles may be prepared by template the shape of dendritic cells.
  • the non-spherical core particle may have an elliptical, rod-shaped, plate-shaped or irregular shape.
  • the non-spherical core particle may be a one-dimensional or two-dimensional nanostructure.
  • the surface of the non-spherical core particle may be negatively charged.
  • the surface of the non-spherical core particle may form a bond with at least one component included in the shell.
  • the non-spherical core particles are organic polymer nanoparticles, metal organic framework nanoparticles, metal nanoparticles, metal oxide nanoparticles, solid lipid nanoparticles, magnetic nanoparticles, It may be one or two or more selected from the group consisting of photothermal conversion nanoparticles, nucleic acid-containing nanoparticles, and protein-containing nanoparticles.
  • the non-spherical core particles may have an average particle diameter of 50 nm to 50 ⁇ m.
  • the non-spherical core particle may have an aspect ratio of 1.1 to 6.0.
  • the shell may further include a component derived from a cell membrane of a cell different from dendritic cells.
  • the surface of the shell may be labeled with a physiologically active polymer, physiologically active component or protein.
  • the method for manufacturing a dendritic cell-mimicking structure includes (S10) purifying a cell membrane from dendritic cells; (S20) forming a cell membrane suspension by treating the cell membrane with ultrasonic waves; (S30) filtering the cell membrane suspension through a membrane filter to obtain liposomes; and (S40) mixing the non-spherical core particles and the liposomes, and then performing filter compression to obtain non-spherical particles having a cell membrane introduced therein.
  • a step of negatively charging the surface of the non-spherical core particle may be further included.
  • the dendritic cell-mimicking structure according to the present disclosure introduces the antigen-presenting ability to the surface of the nanoparticle as it is, and the antigen-presenting function of the dendritic cell is preserved and at the same time, it is not killed, and the targeting function and the photothermal effect function of the nanoparticle are additionally imparted and strengthened. It can provide a functional immuno-anticancer treatment effect.
  • the dendritic cell-mimicking structure according to the present disclosure can provide an effect of increasing an immune response by staying in the body for a long period of time and continuously inducing proliferation and differentiation of T cells.
  • the dendritic cell-mimicking structure according to the present disclosure has the advantage of minimizing side effects through a method of stimulating the patient's own immune system and selectively removing cancer cells of a microscopic size or metastasis that are difficult to diagnose.
  • the dendritic cell-mimicking structure according to the present disclosure has anticancer activity by itself and can be used as an immunotherapeutic agent, and stronger anticancer activity can be expected through combination with other anticancer agents, so it is useful for the development of new anticancer agents that exhibit strong anticancer effects. can be utilized
  • the dendritic cell-mimicking structure according to the present disclosure is designed as a structure to minimize uptake due to being recognized as an external antigen by immune cells in the body, so that the activation effect of cytotoxic T cells is more excellently realized and the immunotherapeutic effect is further strengthened. can provide.
  • Rods 1 to 5 have different colors, and accordingly, UV-Vis absorption wavelengths are all different.
  • FIG. 3 is a graph showing the results of ICP-MS analysis of gold nanorod particles prepared according to Preparation Example 1 of the present invention. It can be confirmed that a sufficient amount of particles was produced at a concentration of 50 ⁇ g/ml or more for all of Rods 1 to 5.
  • GNRs gold nanorods
  • Canton GNRs negatively charged particles
  • 5 is a graph showing the results of analyzing cell viabilit of Rods 1 to 3 after CTAB treatment and citration.
  • FIG. 6 shows a TEM image of gold nanorods coated with a dendritic cell membrane.
  • DC dendritic cells
  • BMDC bone marrow dendritic cells
  • DC rod3 dendritic cell membrane-coated gold nanorods
  • Numerical ranges include lower and upper limits and all values within that range, increments logically derived from the form and breadth of the range being defined, all values defined therein, and the upper and lower limits of the numerical range defined in different forms. includes all possible combinations of Unless otherwise specifically defined in the specification of the present invention, values outside the numerical range that may occur due to experimental errors or rounding of values are also included in the defined numerical range.
  • AR aspect ratio
  • nanoparticle or “nanostructure” may refer to a length, width or diameter ranging from 1 nm to 50 ⁇ m.
  • the dendritic cell-mimicking structure according to the present disclosure preserves the antigen-presenting function of dendritic cells by introducing the antigen-presenting ability of dendritic cells to the surface of nanoparticles, and at the same time significantly increases immune anti-cancer treatment through the targeting function and photothermal effect of nanoparticles. to provide an effect.
  • DC Dendritic cells
  • APCs antigen presenting cells
  • naive T cells naive ell
  • MHC I/II major histocompatibility complex I/II
  • co-stimulatory molecules such as CD80 and CD86
  • cell adhesion molecules such as ICAM-1
  • a dendritic cell-mimicking structure for implementing the antigen presenting function of dendritic cells includes non-spherical core particles; And a shell comprising a cell membrane of lipid molecules derived from dendritic cells; the shell may be characterized in that it includes a bilayer of the lipid molecules.
  • Dendritic cells are present in peripheral tissues, receive activation signals by external stimulation signals, and mature. At the same time, external protein antigens are presented to MHC class I and II in the form of peptides. Thereafter, dendritic cells migrate to the draining lymphnode, bind to T cells having a T cell receptor (TCR) that can bind to the MHC-peptide complex on the surface of dendritic cells, and express CD80, CD86, etc. in dendritic cells. Costimulatory ligands complete activation of T cells by co-binding with CD28, a costimulatory receptor expressed on T cells. Activated T cells proliferate and differentiate, migrate from lymph nodes to peripheral tissues, and can eliminate cells expressing foreign antigens (eg, cancer cells).
  • TCR T cell receptor
  • the dendritic cell-mimicking structure according to the present disclosure functions as a strong T cell activator for activating the cellular immune function, and can further act as an immune cell therapeutic agent.
  • Non-spherical core particles according to the present disclosure may be one-dimensional or two-dimensional nanostructures.
  • Specific examples of the one-dimensional or two-dimensional nanostructures include carbon nanoribbons, carbon nanotubes, graphene, graphene oxide, reduced graphene oxide, MXene, metal nanorods, metal nanowires, or metal nanoplatelets ( platelet), but is not limited thereto.
  • non-spherical core particles include biocompatible organic polymer nanoparticles, metal organic framework nanoparticles, metal nanoparticles, metal oxide nanoparticles, solid lipid nanoparticles, magnetic nanoparticles, and light-to-heat conversion nanoparticles.
  • it may be one or two or more selected from the group consisting of nucleic acid-containing nanoparticles and protein-containing nanoparticles.
  • the nanomaterial itself has no toxicity and has photosensitivity, so that it can be applied to photothermal therapy.
  • organic polymer nanoparticles include polyacetylene, polyaniline, polypyrrole, polythiophene, poly(1,4-phenylenevinylene), poly(1,4-phenylene sulfide), and poly(fluorenylene). tinylene) and at least one selected from the group consisting of derivatives thereof.
  • metal nanoparticles include copper (Cu), nickel (Ni), cobalt (Co), iron (Fe), zinc (Zn), titanium (Ti), chromium (Cr), silver (Ag), gold It may be at least one selected from the group consisting of (Au), platinum (Pt), aluminum (Al), and composites thereof.
  • the metal oxide nanoparticles may be single metal oxide nanoparticles or multi-metal oxide nanoparticles, and the metal may be at least one selected from cerium (Ce), manganese (Mn), and iron (Fe).
  • a ligand compound such as albumin or dextran may be additionally coupled for dispersibility in vivo.
  • the non-spherical core particle may be elliptical, rod-shaped, plate-shaped or irregular.
  • the uptake by macrophages increases as the particle size is larger and the particle is closer to a spherical shape.
  • the dendritic cell-mimicking structure including a shell including non-spherical core particles and a dendritic cell-derived cell membrane can be designed as a structure to minimize the uptake rate by immune cells according to recognition as a foreign antigen when introduced into the body. .
  • Non-spherical core particles according to the present disclosure may have an average particle diameter of 50 nm to 50 ⁇ m, 60 to 1000 nm, or 80 to 500 nm.
  • the non-spherical core particle may be a one-dimensional nanostructure, and the aspect ratio (length/width) of the non-spherical core particle may have a value greater than 1.
  • the aspect ratio is 1.1 to 10.0, 1.1 to 8,0, 1,1 to 6.0, 1.2 to 10.0, 1.2 to 8.0, 1.2 to 6.0, 1.5 to 10.0, 1.5 to 8.0, 1.5 to 6.0, 2.0 to 6.0 or 2.0 to 2.0. May be 5.0.
  • the non-spherical core particle may be a gold nanorod, and may have a maximum absorption wavelength of 700 to 800 nm.
  • the non-spherical core particle has a non-spherical shape and has the maximum absorption wavelength as described above, it is possible to minimize uptake by macrophages and maximize T cell activation.
  • the non-spherical core particles may be gold nanoparticles that can maintain a safe state in the body and are easily surface-modified, but are not limited thereto.
  • the shell formed on the outside of the non-spherical core particle may include a cell membrane of lipid molecules derived from dendritic cells, and may specifically include a bilayer of lipid molecules.
  • the first lipid molecule layer facing the outside of the shell may be oriented to exhibit a stronger negative charge compared to the second lipid molecule layer facing the surface of the non-spherical core particle.
  • the shell containing the cell membrane of the lipid molecule may be thinly and uniformly coated on the surface of the non-spherical core particle in the range of 2 to 50 nm, narrowly 5 to 20 nm.
  • the surface of the non-spherical core particle may be negatively charged for improved colloidal stability when the lipid molecule is coated with the cell membrane.
  • Methods known in the art can be used to obtain negatively charged non-spherical core particles.
  • a particle with a negatively charged surface can be obtained through citric acid treatment.
  • the surface of the non-spherical core particle may form a bond with at least one component included in the shell.
  • the bond may be a variety of chemical bonds such as a covalent bond, an ionic bond, or a complex.
  • the shell may further include components derived from cell membranes of cells different from dendritic cells.
  • the surface of the shell may be labeled with a bioactive polymer, a bioactive component, or a protein.
  • the physiologically active component may mean a cytokine for cell signaling.
  • Non-limiting examples may include chemokines, interferons, interleukins, lymphokines, tumor necrosis factors, monokines and colony stimulating factors.
  • cytokines include BMP (Bone morphogenetic protein) family, CCL (Cheomkine ligands) family, CMTM (CKLF-like MARVEL transmembrane domain containing member) family, CXCL (C-X-C motif ligand ligand) family, GDF (Growth/differentiation factor) family, growth hormone, IFN (Interferon) family, IL (Interleukin) family, TNF (Tumor necrosis factors) family, GPI (glycophosphatidylinositol), SLUPR-1 (Secreted Ly-6/uPAR-Related Protein 1), SLUPR-2 ( Secreted Ly-6/uPAR-Related Protein 2) and combinations thereof.
  • BMP Bone morphogenetic protein
  • CCL Cheomkine ligands
  • CMTM CKLF-like MARVEL transmembrane domain containing member
  • CXCL C-X-C motif ligand ligand
  • the cytokine induces or inhibits transcription factors or growth factors essential for the differentiation of T cells, and mediates the growth and differentiation of other immune cells, thereby further enhancing the effect of immunotherapeutic treatment of the dendritic cell-mimicking structure according to the present disclosure.
  • the dendritic cell-mimicking structure according to the present disclosure may be used for various purposes such as cancer treatment, treatment or prevention of immune diseases, and may be specifically provided in the form of a pharmaceutical composition for cancer treatment.
  • cancer is a general term for various malignant solid tumors that are expandable through local and metastasis by invasion, and specific examples include B-cell lymphoma, non-small cell lung cancer, small cell lung cancer, basal cell carcinoma, and squamous cell carcinoma of the skin. , colorectal cancer, melanoma, head and neck squamous cancer, hepatocellular carcinoma, gastric cancer, sarcoma, gastroesophageal cancer, renal cell carcinoma, glioblastoma, pancreatic cancer, bladder cancer, prostate cancer, breast cancer, cutaneous T-cell lymphoma, Merkel cell carcinoma, or multiple myeloma may, but is not limited thereto.
  • the pharmaceutical composition for treating cancer is used to modify, maintain or preserve pH, osmoticity, viscosity, sterility, transparency, color, isotonicity, odor, stability, dissolution rate or release rate, adsorption or penetration.
  • Formulation materials may be included.
  • the pharmaceutical composition may be administered orally or parenterally.
  • parenteral administration include intravenous, intramuscular, subcutaneous, intraorbital, intracapsular, intraperitoneal, intrarectal, intracisternal, intravascular, and intradermal administration to a patient, and may be administered to a patient through a skin patch or transdermally. It can also be administered through the skin using iontophoresis, respectively.
  • the present disclosure may provide a method for preparing a dendritic cell mimic structure.
  • the dendritic cell-mimicking nanostructure according to the present disclosure is prepared by extracting cell membranes of activated dendritic cells and filter extruding them together with the nanoparticles to induce the cell membranes to be introduced onto the surface of the nanoparticles.
  • (S10) purifying cell membranes from dendritic cells; (S20) forming a cell membrane suspension by treating the cell membrane with ultrasonic waves; (S30) filtering the cell membrane suspension through a membrane filter to obtain liposomes; and (S40) mixing the non-spherical core particles and the liposomes, and then performing filter compression to obtain non-spherical particles having a cell membrane introduced therein.
  • Purifying cell membranes from dendritic cells may be performed through rapid freezing-thawing and centrifugation. Thereafter, the purified cell membrane may be treated with ultrasonic waves to form a cell membrane suspension of hundreds of nanometers or several micrometers. When the cell membrane suspension is filtered through a membrane filter, cell membrane liposomes having a desired size can be obtained.
  • the prepared nonspherical core particles and cell membrane liposomes are mixed and filter compressed to obtain nonspherical core-shell particles into which cell membranes have been introduced. That is, a form in which the cell membrane of dendritic cells is coated on the surface of the non-spherical core particle is obtained.
  • (S50) pulsing the antigen to the non-spherical particles into which the cell membrane has been introduced; further including, a dendritic cell-mimicking functional structure that functions as a dendritic cell can be completed.
  • the step of pulsing the antigen into the nanoparticle into which the cell membrane is introduced is a step in which the antigen is loaded on the cell membrane by exposing the dendritic non-spherical particle to the antigen, which can induce activation of strong antigen-specific T cells. there is.
  • the antigen may be a tumor antigen-derived peptide or protein, and the tumor antigen may be a tumor-associated antigen or a tumor-specific antigen.
  • the tumor antigen may be a protein or peptide derived from ovalbumin (OVA), lymphocytic choriomeningitis mammarenavirus (LCMV) glycoprotein, or retrovirus protein. More specifically, it may be a cancer antigen peptide or protein of OVA257-264, GP33-41, or p15E models.
  • OVA ovalbumin
  • LCMV lymphocytic choriomeningitis mammarenavirus
  • retrovirus protein More specifically, it may be a cancer antigen peptide or protein of OVA257-264, GP33-41, or p15E models.
  • the antigen in human cancer antigens, (1) HER2/Neu, tyrosinase, gp100, MART, HPV E6/E7, EBV EBNA-1, carcinoembryonic antigen, a-fetoprotein, GM2, GD2, testis antigen, prostate antigen, and CD20 and (2) tumor-specific antigens including neoantigens that can be produced by various mutations.
  • the antigen may be one or two or more different peptides of the aforementioned cancer antigen peptide.
  • the pulsing may be performed by various pulsing protocols known in the art, but more preferably, pulsing may be performed by mixing the tumor antigen-derived peptide or protein with a tumor antigen-derived peptide or protein for 0.5 to 6 hours under 5% CO 2 and 37° C. humidified conditions.
  • the antigen when treating OVA 257-264 and GP 33-41 antigens, 0.1 to 0.3 ⁇ g / ml, and when treating p15E antigen, treatment at a concentration of 2 to 7 ⁇ g / ml , the antigen can be pulsed by storing in a 37° C. incubator for 30 minutes after treatment.
  • the antigen-pulsed dendritic cell-mimicking functional construct has excellent cancer targeting function due to its nano-sized size, is stable, and has a large surface area to volume ratio, so it can easily contact T cells. Therefore, an effective anti-cancer immune response can be induced through the activation of the dendritic cell-mimicking functional structure and the activation of the specific T cell response accordingly. In addition, since there is no risk of death in the body, there is an advantage that the circulation time in the body is very long.
  • the dendritic cell-mimicking functional structure according to the present disclosure is prepared by fusing a liposome prepared by sonicating a dendritic cell-derived cell membrane and nanoparticles, and the fusion may mean mixing and co-extruding the liposome and the nanoparticle. .
  • the dendritic cell-derived cell membrane After ultrasonic treatment of the dendritic cell-derived cell membrane, it is filtered through a nano-sized membrane filter to obtain liposomes having a particle size of 200 nm or less.
  • the particle diameter of the liposome may be specifically 50 to 150 nm.
  • the surface zeta potential of the dendritic cell-mimicking nanostructure according to the present disclosure may be -40 to -20 mV, specifically -35 to -25 mV.
  • the present disclosure may provide a drug delivery system or device including the above-described dendritic cell-mimicking nanostructure.
  • the present disclosure may provide a pharmaceutical composition comprising the above-described dendritic cell-mimicking nanostructure and a pharmaceutically acceptable carrier or excipient.
  • a suspension obtained by diluting 40 ml of CTAB-GNR with water was concentrated in an ultrafiltration cell using a membrane filter, the residue was diluted in water, and the suspension was centrifuged again.
  • the residue was redispersed in 0.15% by weight of Na-PSS, the suspension was centrifuged again, and the residue was redispersed in 0.7% by weight of Na-PSS to obtain PSS-stabilized gold nanorods (PSS-GNR).
  • PSS-GNR PSS-stabilized gold nanorods
  • Gold nanorods whose surface is negatively charged after citric acid treatment have a surface potential of -30 to -40 mV in distilled water, so that coating can be achieved through interaction with cell membranes without problems due to electrostatic repulsion, and without aggregation. It can stably retain its shape.
  • FIG. 5 shows the results of evaluating the cell viability of human dermal fibroblasts with respect to CTAB-GNR and citric acid-treated gold nanorods.
  • Cell viability which was as low as 40% or less, reached 100% after treatment with citric acid, confirming that most of the cell toxicity was removed.
  • the dendritic cell mimic structure has a length-width of [1] 110 nm to 20 nm (Aspect Ratio 5.5), [2] 120 nm to 65 nm (Aspect Ratio 1.85), [3] 60 nm to 20 nm (Aspect Ratio 3.5) , [4] 180 nm ⁇ 100 nm (Aspect Ratio 1.8), and [5] 135 nm ⁇ 75 nm (Aspect Ratio 1.8) that a cell membrane coating having a thickness of about 10-20 nm is formed on the surface of the gold nanorod You can check.
  • the surface charge was confirmed by measuring the zeta potential of the dendritic cell membrane (DC), the dendritic cell mimicking structure (Rod1 to Rod5) and the spherical dendritic cell mimicking structure (S60), and the results are shown in FIG. 7 .
  • the strong negative zeta potential of the gold nanorods dispersed with citric acid before coating the dendritic cell membrane shows a relatively low value after coating the cell membrane.
  • potential values similar to those of the dendritic cell membrane were shown, confirming that the cell membrane coating was successfully performed.

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Abstract

La présente invention concerne une structure fonctionnelle imitant une cellule dendritique comprenant : une particule noyau non sphérique ; et une enveloppe comprenant une membrane cellulaire de molécules lipidiques dérivées d'une cellule dendritique, et son procédé de production, la structure fonctionnelle imitant une cellule dendritique atteignant de manière significative l'effet d'activation stable des lymphocytes T dans le corps, et peut ainsi fournir un effet de traitement immuno-anticancéreux amélioré.
PCT/KR2022/020615 2021-12-16 2022-12-16 Nanostructure fonctionnelle imitant une cellule dendritique, et son procédé de production WO2023113550A1 (fr)

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KR1020220176132A KR20230091817A (ko) 2021-12-16 2022-12-15 수지상세포 모방 기능성 나노구조체 및 이의 제조방법
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Citations (4)

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