PEGylated liposomes encapsulating human hemoglobin enhance oxygen transfer and cell proliferation while decreasing cell hypoxia in fibrin

Oxygen supply to cells in three-dimensional cultures occurs mainly by diffusion, with insufficient oxygen concentration reaching the center of cell aggregates, thus creating hypoxic areas and leading eventually to cell death. The aims of this study were, firstly to measure and characterize the oxygen transfer from liposomes encapsulating human hemoglobin (LEH) to an aqueous environment and, secondly, to study the effects of LEH to cells grown in a three-dimensional environment. LEH were loaded with pure oxygen and the oxygen transfer from the liposomes to an aqueous phase was monitored. Human umbilical vein endothelial cells (HUVEC) were cultured in a fibrin gel mimicking a diffusion-limited environment. After 24 h, HUVEC seeded in fibrin covered with culture medium supplemented with oxygen-loaded LEH showed a decrease in HIF-1α expression and an increase in proliferation compared to those in fibrin cultured either with medium containing liposomes with no hemoglobin or non-modified medium.

► Liposomes encapsulating hemoglobin enhance oxygen transfer.
► Liposomes encapsulating hemoglobin enhance cell proliferation in fibrin.
► Liposomes encapsulating hemoglobin reduce HIF-1α (hypoxia) expression in cells grown in fibrin.