Vasandani V M, Madan S, Ghosh P C
Department of Biochemistry, University of Delhi South Campus, India.
Biochim Biophys Acta. 1992 Jun 12;1116(3):315-23. doi: 10.1016/0304-4165(92)90046-w.
Monensin, a carboxylic ionophore, which is known to raise intravesicular pH, was intercalated in liposomes and its effect on the toxicity of ricin in mice was studied. The toxicity of ricin in vivo was found to be significantly enhanced by the administration of monensin intercalated in liposomes (liposomal monensin). The observed enhancement of the toxicity of ricin by monensin was highly dose-dependent and was maximal when ricin was injected within 60 min of monensin injection. The survival time was found to be reduced in the range of 8-20 h, depending on the dose of ricin used, by liposomal monensin. Stability of liposomes containing monensin as inferred from the release of entrapped calcein or FITC-dextran under both in vivo and in vitro conditions was comparable to that observed for liposomes without monensin. Liposomal monensin remains in circulation for 2 h and was cleared from the blood stream after 4 h. In contrast, 15 min was required for the clearance of monensin when administered in free form. Studies on the distribution of liposomal monensin and 125I-ricin in various tissues have revealed that monensin is mainly localized in the liver and spleen which are also the major sites for ricin accumulation. Our observation on the substantial enhancement of ricin toxicity in vivo by liposomal monensin strongly supports the potential usefulness of the latter as a potentiating agent in the enhancement of the toxicity of immunotoxin or hormonotoxin for selective elimination of cancer cells.
莫能菌素是一种羧酸离子载体，已知其可提高囊泡内的pH值，将其嵌入脂质体中，并研究了其对蓖麻毒素在小鼠体内毒性的影响。发现通过给予嵌入脂质体的莫能菌素（脂质体莫能菌素），蓖麻毒素在体内的毒性显著增强。观察到莫能菌素对蓖麻毒素毒性的增强具有高度剂量依赖性，并且当在注射莫能菌素后60分钟内注射蓖麻毒素时毒性最大。根据所使用的蓖麻毒素剂量，脂质体莫能菌素可使存活时间缩短8 - 20小时。从体内和体外条件下包裹的钙黄绿素或异硫氰酸荧光素 - 葡聚糖的释放情况推断，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。脂质体莫能菌素在循环中停留2小时，4小时后从血流中清除。相比之下，以游离形式给药时，莫能菌素清除需要15分钟。对脂质体莫能菌素和125I - 蓖麻毒素在各种组织中的分布研究表明，莫能菌素主要定位于肝脏和脾脏，而这也是蓖麻毒素积累的主要部位。我们关于脂质体莫能菌素在体内显著增强蓖麻毒素毒性的观察结果有力地支持了后者作为增强免疫毒素或激素毒素毒性以选择性消除癌细胞的增效剂的潜在用途。
