Phagocytosis of poly L-lysine-graft-poly ethylene glycol coated microspheres by antigen presenting cells: Impact of grafting ratio and poly ethylene glycol chain length on cellular recognitionReport as inadecuate




Phagocytosis of poly L-lysine-graft-poly ethylene glycol coated microspheres by antigen presenting cells: Impact of grafting ratio and poly ethylene glycol chain length on cellular recognition - Download this document for free, or read online. Document in PDF available to download.

Biointerphases

, Volume 1, Issue 4, pp 123–133

Received: 11 July 2006Accepted: 10 November 2006

Abstract

Microparticulate carrier systems have significant potential for antigen delivery. The authors studied how microspheres coated with the polycationic copolymer polyL-lysine-graft-polyethylene glycol PLL-g-PEG can be protected against unspecific phagocytosis by antigen presenting cells, a prerequisite for selective targeting of phagocytic receptors. For this aim the authors explored the influence of PLL-g-PEG architecture on recognition of coated microspheres by antigen presenting cells with regard to both grafting ratio and molecular weight of the grafted PEG chains. Carboxylated polystyrene microspheres 5 μm were coated with a small library of PLL-g-PEG polymers with PLL backbones of 20 kDa, grafting ratios from 2 to 20, and PEG side chains of 1–5 kDa. The coated microspheres were characterized by their ζ-potential and resistance to IgG adsorption. Phagocytosis of these microspheres by human monocyte derived dendritic cells DCs and macrophages MΦ was quantified by phase contrast microscopy and by analysis of the cells’ side scattering in a flow cytometer. Generally, increasing grafting ratios impaired the protein resistance of coated microspheres, leading to higher phagocytosis rates. For DC, long PEG chains of 5 kDa decreased the phagocytosis of coated microspheres even in the case of considerable IgG adsorption. In addition, preferential adsorption of dysopsonins is discussed as another factor for decreased phagocytosis rates. For comparison, the authors studied the cellular adhesion of DC and Mζ to PLL-g-PEG coated microscopy slides. Remarkably, DC and Mζ were found to adhere to relatively protein-resistant PLL-g-PEG adlayers, whereas phagocytosis of microspheres coated with the same copolymers was inefficient. Overall, PLL20-3.5-PEG2 was identified as the optimal copolymer to ensure resistance to both phagocytosis and cell adhesion. Finally, the authors studied coatings made from binary mixtures of PLL-g-PEG type copolymers that led to microspheres with combined properties. This enables future studies on cell targeting with ligand modified copolymers.

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Author: Uta Wattendorf - Mirabai C. Koch - Elke Walter - Janos Vörös - Marcus Textor - Hans P. Merkle

Source: https://link.springer.com/







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