Endocytosis of poly(ethylene sodium phosphate) by macrophages and the effect of polymer length on cellular uptake

Abstract

Phosphorus-containing polymers are taking a growing interest as a bio-applicable material. Anionic poly(phosphodiester) is one type of phosphorus-containing polymer and has a similar backbone structure to teichoic acid (TA), which makes up the cell walls of gram-positive bacteria. In this study, we synthesized a copolymer of ethylene sodium phosphate and butynyl phosphate (P(EP⋅Na/BYP)), which mimics TA and, thus, should be taken up by macrophages by the same mechanism as bacterial cells. In-vitro studies showed that RAW 264.7 mammalian macrophages exhibited higher uptake of P(EP⋅Na/BYP) than L929 mammalian fibroblasts. Further, the uptake of P(EP⋅Na/BYP) by macrophages decreased in the presence of dextran sulfate; this implies that the scavenger receptor contributes to endocytosis of P(EP·Na/BYP). In-vitro studies on P(EP·Na/BYP) with different lengths (38, 85, and 127 phosphate residues) showed that P(EP·Na/BYP) with 127 phosphate residues led to the highest intracellular transportation and the least gene expressions of IL-6 and TNF-α. These results demonstrate that water-soluble poly(phosphodiester) can be used as a modifier to deliver medical drugs to macrophages.