Evaluation of Phosphatidylserine-Specific Peptide-Conjugated Liposomes Using a Model System of Malaria-Infected Erythrocytes.

Malaria is one of the most prevalent parasitic diseases and is most widespread in tropical regions. The malarial parasite grows and reproduces in erythrocytes during its life cycle, resulting in programmed erythrocyte death, termed eryptosis. Lipid scrambling, which occurs following the exposure of anionic lipids such as phosphatidylserine (PS) on the outer surface of erythrocytes, is a characteristic physical change that occurs early during eryptosis. Here, we prepared "PS specific peptide (PSP)"-conjugated liposomes (PSP-liposomes) and investigated whether PSP-liposomes hold promise as a novel strategy for actively targeting eryptosis. Eryptosis was induced by exposing red blood cells (RBCs) to ionomycin, a known calcium ionophore. When PSP liposomes were mixed with either RBCs or RBCs undergoing eryptosis (E-RBCs), the amount of PSP-liposome bound to E-RBCs was much higher than the amount bound to RBCs. However, the amount of PSP-liposome bound to E-RBCs was significantly inhibited by the presence of annexin V protein, which binds specifically to PS. These results suggest that PSP-liposomes could be an effective drug nanocarrier for treating E-RBCs and malaria-infected erythrocytes.