• 专利标题:   Self-assembled graphene quantum dot nano-particle in fluorescence imaging medicine, comprises graphene quantum dot-polyethylene glycol-adamantane/cyclodextrin-multi-arm polyethylene diol carrier, multi-arm polyethylene glycol and cyclodextrin are covalently linked.
  • 专利号:   CN114848852-A, CN114848852-B
  • 发明人:   WANG B, YANG Y, ZHOU X
  • 专利权人:   CAS INNOVATION ACAD PRECISION MEASUREMEN, INNOVATION ACAD PRECISION MEASUREMENT
  • 国际专利分类:   A61K041/00, A61K047/52, A61K047/60, A61K047/69, A61K049/00, A61K049/12, A61K049/18, A61P035/00
  • 专利详细信息:   CN114848852-A 05 Aug 2022 A61K-049/00 202287 Chinese
  • 申请详细信息:   CN114848852-A CN10076014 20 Jan 2021
  • 优先权号:   CN10076014

▎ 摘  要

NOVELTY - Self-assembled graphene quantum dot nanoparticle comprises a graphene quantum dot-polyethylene glycol-adamantane/cyclodextrin-multi-arm polyethylene diol carrier, multi-arm polyethylene glycol and cyclodextrin are covalently linked, where the molar ratio of multi-arm polyethylene glycol and cyclodextrin is 5 μmol: 400 μmol, the cyclodextrin is 6-benzenesulfonic acid-β-cyclodextrin. The average molecular weight of the multi-arm polyethylene glycol is 10KDa, the polyethylene glycol is a straight chain structure, the average molecular weight is 2KDa, and the adamantane and graphene quantum dots are covalently connected to both ends of the polyethylene glycol respectively. The reaction molar ratio of polyethylene glycol and adamantane is 0.1:1, the reaction mass ratio of graphene quantum dots and polyethylene glycol-adamantane is 15:50 mg. USE - Self-assembled graphene quantum dot nano-particle used in fluorescence imaging medicine (claimed) and for cancer treatment research and to the field of biological medicine. DETAILED DESCRIPTION - Self-assembled graphene quantum dot nanoparticle comprises a graphene quantum dot-polyethylene glycol-adamantane/cyclodextrin-multi-arm polyethylene diol carrier, multi-arm polyethylene glycol and cyclodextrin are covalently linked, where the molar ratio of multi-arm polyethylene glycol and cyclodextrin is 5 μmol: 400 μmol, the cyclodextrin is 6-benzenesulfonic acid-β-cyclodextrin. The average molecular weight of the multi-arm polyethylene glycol is 10KDa, the polyethylene glycol is a straight chain structure, the average molecular weight is 2KDa, and the adamantane and graphene quantum dots are covalently connected to both ends of the polyethylene glycol respectively. The reaction molar ratio of polyethylene glycol and adamantane is 0.1:1, the reaction mass ratio of graphene quantum dots and polyethylene glycol-adamantane is 15:50 mg, and the ratio of graphene quantum dots-polyethylene glycol-adamantane and cyclodextrin-multi-arm polyethylene glycol self-assembled is 1:1. An INDEPENDENT CLAIM is included for a method for preparing a self-assembled graphene quantum dot nanoparticle, which involves: a. dissolving 1-adamantanoyl chloride and Boc-polyethylene glycol-ammine in anhydrous dichloromethane, adding catalytic amount of triethylamine and stirring at room temperature overnight, removing dichloromethane by rotary evaporation, dissolving residue in water and centrifuged to remove the precipitate, adding supernatant 1/10 of the volume of trifluoroacetic acid to the solution and stirred overnight, evaporating obtained solution to remove trifluoroacetic acid and adding to the graphene quantum dot solution, adding condensing agent EDC, NHS and catalytic triethylamine, stirring the mixture at room temperature for 48 hours to obtain graphene quantum dots-polyethylene glycol-adamantane, which is denoted as GQD-PEG-Ad; b. dissolving multi-arm polyethylene glycol and 6-benzenesulfonic acid-β-cyclodextrin in DMSO, and reacting at 70℃ for 72 hours; c. dialyzing ultrapure water for 72 hours to remove DMSO, that is, multi-arm polyethylene glycol-cyclodextrin, which is recorded as mPEG-CD; d. adding same volume and equal concentration of mPEG-CD aqueous solution to the GQDs-PEG-Ad aqueous solution and stirring for 12 hours to complete the hydrophilic and hydrophobic self-assembly of adamantane and cyclodextrin in the aqueous phase to obtain self-assembled graphene quantum dot nanoparticles, Denoted as GQD NP, where the molecular weight of Boc-PEG-NH2is 2KDa, and the molecular weight of m-polyethylene glycol-NH2is 10KDa and obtaining gaphene quantum dots by oxidizing hydroxylated carbon nanotubes, and e. dissolving small molecule drug containing the conjugated structure in DMSO (dimethyl sulfoxide), and adding same volume of GQD-PEG-Ad aqueous solution, placing on a shaker for 24 hours at a speed of 300 rpm, adding mPEG-CD aqueous solution and stirring for 12 hours, and then separating a removing dimethyl sulfoxide and residual small molecule drugs to obtain product.