Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies.
Effect of liposome composition and other factors on the targeting of liposomes to experimental tumors: biodistribution and imaging studies.
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发表时间：
1990-10
期刊：
影响因子：
11.2
通讯作者：
A. Gabizon;D. Price;J. Huberty;R. Bresalier;D. Papahadjopoulos
中科院分区：
文献类型：
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作者：
A. Gabizon;D. Price;J. Huberty;R. Bresalier;D. Papahadjopoulos
我们检查了静脉注射后放射性标记脂质体在荷瘤小鼠中的分布。两个小鼠肿瘤（B16黑色素瘤，J6456淋巴瘤）和一个人肿瘤（LS 174 T结肠癌）经肌肉注射接种，s.c.，或在后足垫中。当使用放射性标记的镓-67-去铁胺比较平均囊泡直径约为100 nm的各种脂质体组合物时，用含有高相变温度的磷脂酰胆碱和小摩尔分数的单唾液酸神经节苷脂或氢化磷脂酰肌醇（HPI）的脂质体获得最佳肿瘤定位。在注射后24小时，可重复地获得高于10%注射剂量/g的肿瘤摄取平均值和接近1的肝肿瘤比。将HPI的摩尔分数从总磷脂的9%增加到41%导致肝摄取增强和肿瘤摄取减少。影响囊泡大小的方法学方面似乎显著影响脂质体在肿瘤中的定位。然而，在10倍范围内改变磷脂剂量仅引起肿瘤中回收的注射剂量百分比的微小变化。在含单唾液酸神经节苷脂和HPI的脂质体中使用其他放射性标记[[3 H]菊粉和铟-111-标记的博来霉素（111 In-Bleo）]也观察到肿瘤的高摄取。在111 In-Bleo的情况下，脂质体中的包封导致注射后24小时放射性标记的肿瘤蓄积增加约20至40倍。通过镓-67-去铁胺和111 In-Bleo标记的脂质体的成像实验，也记录了接种肿瘤的小鼠足垫中脂质体的显著定位，而不是对侧模拟注射的足垫。这些结果支持以下论点：先前显示具有长循环半衰期的一些含糖脂的脂质体在各种肿瘤中显著累积，并且是用于递送抗肿瘤剂的有希望的工具。
We have examined the distribution of radiolabeled liposomes in tumor-bearing mice after i.v. injection. Two mouse tumors (B16 melanoma, J6456 lymphoma) and a human tumor (LS174T colon carcinoma) inoculated i.m., s.c., or in the hind footpad were used in these studies. When various liposome compositions with a mean vesicle diameter of approximately 100 nm were compared using a radiolabel of gallium-67-deferoxamine, optimal tumor localization was obtained with liposomes containing a phosphatidylcholine of high phase-transition temperature and a small molar fraction of monosialoganglioside or hydrogenated phosphatidylinositol (HPI). At 24 h after injection, average values of tumor uptake higher than 10% of the injected dose per g and liver-to-tumor ratios close to 1 were reproducibly obtained. Increasing the molar fraction of HPI from 9% to 41% of the total phospholipid resulted in enhancement of liver uptake and decrease of tumor uptake. Methodological aspects that influence vesicle size appear to affect significantly liposome localization in the tumor. However, varying the phospholipid dose within a 10-fold range caused only minor changes in the percent of injected dose recovered in the tumor. A high uptake by tumors was also observed using other radiolabels [[3H]inulin and indium-111-labeled bleomycin (111In-Bleo)] in monosialoganglioside- and HPI-containing liposomes. In the case of 111In-Bleo, encapsulation in liposomes resulted in approximately 20- to 40-fold increase in tumor accumulation of the radiolabel at 24 h after injection. The marked localization of liposomes in the mouse footpad inoculated with tumor as opposed to the contralateral mock-injected footpad was also documented by imaging experiments with gallium-67-deferoxamine and 111In-Bleo-labeled liposomes. These results support the contention that some glycolipid-containing liposomes previously shown to have long circulating half-lives accumulate significantly in a variety of tumors and are promising tools for the delivery of anti-tumor agents.