Tagami Tatsuaki, Yanai Hiroshi, Terada Yuka, Ozeki Tetsuya
Drug Delivery and Nano Pharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University.
Biol Pharm Bull. 2015;38(10):1649-51. doi: 10.1248/bpb.b15-00310.
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.
疟疾是最普遍的寄生虫病之一，在热带地区最为流行。疟原虫在其生命周期中于红细胞内生长和繁殖，导致程序性红细胞死亡，即红细胞凋亡。脂质翻转，即在红细胞外表面暴露如磷脂酰丝氨酸（PS）等阴离子脂质后发生的现象，是红细胞凋亡早期出现的一种特征性物理变化。在此，我们制备了“PS特异性肽（PSP）”偶联脂质体（PSP-脂质体），并研究了PSP-脂质体作为一种主动靶向红细胞凋亡的新策略是否具有前景。通过将红细胞（RBC）暴露于已知的钙离子载体离子霉素来诱导红细胞凋亡。当PSP脂质体与RBC或正在经历红细胞凋亡的RBC（E-RBC）混合时，与E-RBC结合的PSP-脂质体数量远高于与RBC结合的数量。然而，与E-RBC结合的PSP-脂质体数量被膜联蛋白V蛋白显著抑制，膜联蛋白V蛋白可特异性结合PS。这些结果表明，PSP-脂质体可能是治疗E-RBC和疟疾感染红细胞的有效药物纳米载体。
