title: Effect of partial PEGylation on particle uptake by macrophages.
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.
authors.affiliation: Department of Chemistry, Indiana University, Bloomington, Indiana 47405, USA. yy33@indiana.edu.
authors.forename: Lucero
authors.initials: L
authors.lastname: Sanchez
authors.forename: Yi
authors.initials: Y
authors.lastname: Yi
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
mesh_terms: D000818:Animals; D001692:Biological Transport; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000378:metabolism*; D010587:Phagocytosis; D011092:Polyethylene Glycols / Q000737:chemistry*; D000067996:RAW 264.7 Cells; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D008024:Ligands; D011092:Polyethylene Glycols