Madan S, Ghosh P C
Department of Biochemistry, University of Delhi South Campus, India.
Biochem Int. 1992 Oct;28(2):287-95.
Monensin, a carboxylic ionophore, which is known to disrupt intracellular trafficking of proteins was intercalated in liposomes and its effect on the stability of liposomes and cytotoxicities of ricin and Pseudomonas exotoxin A in mouse macrophage tumor cells J774A.1 was studied. Stability of liposomes containing monensin was comparable to liposomes without monensin. The cytotoxicity of ricin and Pseudomonas exotoxin A was significantly enhanced by 1nM liposomal monensin (15.7 and 3.6 fold respectively). The enhancing potency of monensin in neutral and negative vesicles was found to be similar, while it was drastically reduced in positive vesicles. The specific uptake of 125I-gelonin from neutral and negative vesicles was not significantly different, whereas from positive vesicles no uptake was observed. Serum strongly influenced the binding at 4 degrees C of positive vesicles as well as the enhancing potency of monensin in these vesicles. Monensin in neutral and negative vesicles significantly reduced the lag period of ricin action, while in positive vesicles, it had no effect. These studies clearly indicate that liposomes could be used as a delivery vehicle for monensin.
莫能菌素是一种羧酸离子载体，已知它会破坏蛋白质的细胞内运输，将其嵌入脂质体中，并研究了其对脂质体稳定性以及蓖麻毒素和铜绿假单胞菌外毒素A在小鼠巨噬细胞肿瘤细胞J774A.1中的细胞毒性的影响。含有莫能菌素的脂质体的稳定性与不含莫能菌素的脂质体相当。1nM脂质体莫能菌素可显著增强蓖麻毒素和铜绿假单胞菌外毒素A的细胞毒性（分别增强15.7倍和3.6倍）。发现莫能菌素在中性和阴性囊泡中的增强效力相似，而在阳性囊泡中则大幅降低。125I-去甲氧基蓖麻毒素从中性和阴性囊泡中的特异性摄取没有显著差异，而从阳性囊泡中未观察到摄取。血清强烈影响阳性囊泡在4℃时的结合以及莫能菌素在这些囊泡中的增强效力。中性和阴性囊泡中的莫能菌素显著缩短了蓖麻毒素作用的延迟期，而在阳性囊泡中则没有作用。这些研究清楚地表明脂质体可作为莫能菌素的递送载体。
