Gregoriadis G, Putman D, Louis L, Neerunjun D
Biochem J. 1974 May;140(2):323-30. doi: 10.1042/bj1400323.
Non-entrapped and liposome-entrapped Clostridium perfringens neuraminidase (0.5-0.6 unit) was injected into rats and its fate as well as its effect on plasma and erythrocyte N-acetylneuraminic acid was investigated. The following observations were made. (1) Although removal of both non-entrapped and liposome-entrapped neuraminidase from the circulation was completed within 5h after injection, their recovery in tissues was distinctly different; 7-10% of the injected non-entrapped enzyme was found in the liver and none in the liver lysosomal fraction or the spleen. In contrast, 20-26% of the liposome-entrapped enzyme was found in the liver of which 60-69% was in the lysosomal fraction. Spleen contained 3.6-5.0% of the enzyme. (2) The presence of the non-entrapped neuraminidase in blood led to the extensive desialylation of plasma and to a decrease in the concentration or total removal from the circulation of some of the plasma glycoproteins. (3) Injection of non-entrapped neuraminidase also led to the partial desialylation of erythrocytes the life span of which was diminished and their uptake by the liver and spleen augmented. (4) Entrapment of neuraminidase in liposomes before its injection prevented the enzyme from acting on its substrate in plasma or on the erythrocyte surface, and values obtained for plasma glycoproteins and erythrocyte survival were similar to those observed in control rats. (5) Entrapment in liposomes of therapeutic hydrolases intended for the degradation of substances stored within the tissue lysosomes of patients with storage diseases could prevent the potentially hazardous enzymic action of hydrolases in blood and at the same time direct the enzymes to the intracellular sites where they are needed.
将非包裹型和脂质体包裹型产气荚膜梭菌神经氨酸酶（0.5 - 0.6单位）注射到大鼠体内，研究其去向以及对血浆和红细胞N - 乙酰神经氨酸的影响。得到以下观察结果：（1）尽管注射后5小时内循环中的非包裹型和脂质体包裹型神经氨酸酶均被清除，但它们在组织中的回收情况明显不同；注射的非包裹型酶有7 - 10%在肝脏中被发现，而在肝脏溶酶体部分或脾脏中未发现。相比之下，脂质体包裹型酶有20 - 26%在肝脏中被发现，其中60 - 69%在溶酶体部分。脾脏中含有3.6 - 5.0%的该酶。（2）血液中存在非包裹型神经氨酸酶导致血浆广泛去唾液酸化，并使一些血浆糖蛋白的浓度降低或从循环中完全清除。（3）注射非包裹型神经氨酸酶还导致红细胞部分去唾液酸化，其寿命缩短，肝脏和脾脏对其摄取增加。（4）在注射前将神经氨酸酶包裹在脂质体中可防止该酶作用于血浆中的底物或红细胞表面，血浆糖蛋白和红细胞存活情况的检测值与对照大鼠相似。（5）将用于降解储存疾病患者组织溶酶体内储存物质的治疗性水解酶包裹在脂质体中，可防止水解酶在血液中产生潜在的有害酶促作用，同时将酶导向细胞内需要它们的部位。
