Engineered hydrogen-bonded glycopolymer capsules and their interactions with antigen presenting cells

Kristian Kempe, Sue D Xiang, Paul Wilson, Md Arifur Rahim, Yi Ju, Michael R Whittaker, David M Haddleton, Magdalena Plebanski, Frank Caruso, Thomas P Davis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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 (SiO2 particles, d = 1.16 μm) yielded stable glycopolymer films upon cross-linking by CuAAC. The silica (SiO2) 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.

Original languageEnglish
Pages (from-to)6444-6452
Number of pages9
JournalACS Applied Materials and Interfaces
Volume9
Issue number7
DOIs
Publication statusPublished - 22 Feb 2017

Keywords

  • CD80
  • dendritic cells
  • layer-by-layer
  • macrophages
  • mannose
  • MDSC
  • PDL-1
  • poly(2-oxazoline)

Cite this

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title = "Engineered hydrogen-bonded glycopolymer capsules and their interactions with antigen presenting cells",
abstract = "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 (SiO2 particles, d = 1.16 μm) yielded stable glycopolymer films upon cross-linking by CuAAC. The silica (SiO2) 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.",
keywords = "CD80, dendritic cells, layer-by-layer, macrophages, mannose, MDSC, PDL-1, poly(2-oxazoline)",
author = "Kristian Kempe and Xiang, {Sue D} and Paul Wilson and Rahim, {Md Arifur} and Yi Ju and Whittaker, {Michael R} and Haddleton, {David M} and Magdalena Plebanski and Frank Caruso and Davis, {Thomas P}",
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Engineered hydrogen-bonded glycopolymer capsules and their interactions with antigen presenting cells. / Kempe, Kristian; Xiang, Sue D; Wilson, Paul; Rahim, Md Arifur; Ju, Yi; Whittaker, Michael R; Haddleton, David M; Plebanski, Magdalena; Caruso, Frank; Davis, Thomas P.

In: ACS Applied Materials and Interfaces, Vol. 9, No. 7, 22.02.2017, p. 6444-6452.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Kempe, Kristian

AU - Xiang, Sue D

AU - Wilson, Paul

AU - Rahim, Md Arifur

AU - Ju, Yi

AU - Whittaker, Michael R

AU - Haddleton, David M

AU - Plebanski, Magdalena

AU - Caruso, Frank

AU - Davis, Thomas P

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N2 - 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 (SiO2 particles, d = 1.16 μm) yielded stable glycopolymer films upon cross-linking by CuAAC. The silica (SiO2) 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.

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KW - CD80

KW - dendritic cells

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KW - macrophages

KW - mannose

KW - MDSC

KW - PDL-1

KW - poly(2-oxazoline)

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DO - 10.1021/acsami.6b15459

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SN - 1944-8244

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