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Issue 1, 2017
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Effect of partial PEGylation on particle uptake by macrophages

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Abstract

Controlling the internalization of synthetic particles by immune cells remains a grand challenge for developing successful drug carrier systems. Polyethylene glycol (PEG) is frequently used as a protective coating on particles to evade immune clearance, but it also hinders the interactions of particles with their intended target cells. In this study, we investigate a spatial decoupling strategy, in which PEGs are coated on only one hemisphere of particles, so that the other hemisphere is available for functionalization of cell-targeting ligands without the hindrance effect from the PEGs. The partial coating of PEGs is realized by creating two-faced Janus particles with different surface chemistries on opposite sides. We show that a half-coating of PEGs reduces the macrophage uptake of particles as effectively as a complete coating. Owing to the surface asymmetry, Janus particles that are internalized enter macrophage cells via a combination of ligand-guided phagocytosis and macropinocytosis. By spatially segregating PEGs and ligands for targeting T cells on Janus particles, we demonstrate that the Janus particles bind T cells uni-directionally from the ligand-coated side, bypassing the hindrance from the PEGs on the other hemisphere. The results reveal a new mechanistic understanding on how a spatial coating of PEGs on particles changes the phagocytosis of particles. This study also suggests a new design principle for therapeutic particles – the spatial decoupling of PEGs and cell-targeting moieties reduces the interference between the two functions while attaining the protective effect of PEGs for macrophage evasion.

Graphical abstract: Effect of partial PEGylation on particle uptake by macrophages

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Publication details

The article was received on 17 Sep 2016, accepted on 23 Nov 2016 and first published on 02 Dec 2016


Article type: Paper
DOI: 10.1039/C6NR07353K
Citation: Nanoscale, 2017,9, 288-297
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    Effect of partial PEGylation on particle uptake by macrophages

    L. Sanchez, Y. Yi and Y. Yu, Nanoscale, 2017, 9, 288
    DOI: 10.1039/C6NR07353K

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