ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University , Parkville, Victoria 3052, Australia.
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
ACS Appl Mater Interfaces. 2017 Feb 22;9(7):6444-6452. doi: 10.1021/acsami.6b15459. Epub 2017 Feb 10.
Hollow glycopolymer microcapsules were fabricated by hydrogen-bonded layer-by-layer (LbL) assembly, and their interactions with a set of antigen presenting cells (APCs), including dendritic cells (DCs), macrophages (MACs), and myeloid derived suppressor cells (MDSCs), were investigated. The glycopolymers were obtained by cascade postpolymerization modifications of poly(oligo(2-ethyl-2-oxazoline methacrylate)-stat-glycidyl methacrylate) involving the modification of the glycidyl groups with propargylamine and the subsequent attachment of mannose azide by copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Multilayer assembly of the hydrogen-bonding pair (glycopolymer/poly(methacrylic acid) (PMA)) onto planar and particulate supports (SiO particles, d = 1.16 μm) yielded stable glycopolymer films upon cross-linking by CuAAC. The silica (SiO) particle templates were removed yielding hollow monodisperse capsules, as demonstrated by fluorescence and scanning electron microscopy. Cellular uptake studies using flow cytometry revealed the preferential uptake of the capsules by DCs when compared to MACs or MDSCs. Mannosylated capsules showed a cytokine independent cis-upregulation of CD80 specifically on DCs and a trans-downregulation of PDL-1 on MDSCs. Thus, the glycopolymer capsules may have potential as vaccine carriers, as they are able to upregulate costimulatory molecules for immune cell stimulation on DCs and at the same time downregulate immune inhibitory receptors on suppressor APC such as MDSCs.
通过氢键层层（LbL）组装制备了中空糖基聚合物微胶囊，并研究了它们与一组抗原呈递细胞（APCs）的相互作用，包括树突状细胞（DCs）、巨噬细胞（MACs）和髓系来源的抑制性细胞（MDSCs）。糖聚合物是通过聚（聚（2-乙基-2-恶唑啉甲基丙烯酸酯）-stat-甲基丙烯酸缩水甘油酯）的级联后聚合修饰获得的，涉及用炔丙胺修饰缩水甘油基，随后通过铜（I）催化的叠氮-炔环加成（CuAAC）将甘露糖叠氮化物连接。将氢键对（糖聚合物/聚（甲基丙烯酸）（PMA））的多层组装到平面和颗粒状载体（SiO 颗粒，d = 1.16 μm）上，通过 CuAAC 交联后可得到稳定的糖聚合物膜。通过荧光和扫描电子显微镜证实，去除硅（SiO）颗粒模板后，可得到中空单分散胶囊。使用流式细胞术进行的细胞摄取研究表明，与 MACs 或 MDSCs 相比，DCs 优先摄取胶囊。甘露糖化胶囊可在 DCs 上独立于细胞因子地 cis 上调 CD80，同时在 MDSCs 上 trans 下调 PDL-1。因此，糖聚合物胶囊作为疫苗载体具有潜力，因为它们能够在 DCs 上上调免疫细胞刺激的共刺激分子，同时下调抑制性 APC（如 MDSCs）上的免疫抑制受体。
