Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice.
Microscopic localization of sterically stabilized liposomes in colon carcinoma-bearing mice.
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发表时间：
1992-10
期刊：
影响因子：
11.2
通讯作者：
Shiying Huang;K. Lee;K. Hong;Friendly Ds;D. Papahadjopoulos
中科院分区：
文献类型：
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作者：
Shiying Huang;K. Lee;K. Hong;Friendly Ds;D. Papahadjopoulos
使用光学和电子显微镜，我们研究了在体内分布的脂质体空间稳定的特定脂质，延长其在血液中的循环。由二硬脂酰磷脂酰胆碱：胆固醇：单唾液酸神经节苷脂GM 1（10：5：1）包封的67 Ga-去铁醛组成的空间稳定脂质体的组织分布表明，在尾静脉注射后24 h，超过30%的脂质体仍然保留在血液中。此外，这种脂质体在肿瘤（皮下植入的C-26结肠癌细胞）中积累，达到与肝脏几乎相同的摄取水平（约20%注射剂量/g组织）。胶体金或罗丹明标记葡聚糖标记的脂质体的显微定位与组织分布一致。为了评价循环参数，注射了两种尺寸的含金卵磷脂：胆固醇：二硬脂酰磷脂酰乙醇胺（在其氨基位置用1900分子量聚乙二醇片段衍生化）（10：5：0.8）脂质体。在脂质体注射后0.5、4和24 h，通过负染色制剂的电子显微镜检查血浆。发现小（小于100 nm直径）与大（大于100 nm）脂质体的比率随时间增加，表明较大脂质体的清除快得多。为了检测脂质体在各种组织中的定位，在注射由卵磷脂酰胆碱：胆固醇：单唾液酸神经节苷脂GM 1（10：5：1）或卵磷脂酰胆碱：胆固醇：衍生化二硬脂酰磷脂酰乙醇胺组成的含金脂质体（直径在80和100 nm之间）后24 h固定适当的样品。本研究检查的组织包括正常肝脏、骨髓和植入肿瘤。银增强胶体金主要存在于正常肝脏的枯否细胞和骨髓的巨噬细胞内。在肝细胞中很少检测到任何银增强的金颗粒。在所有制剂中，电子显微镜检查显示，在肝脏和骨髓中固定窦衬里巨噬细胞的内体和溶酶体中存在金。在植入肿瘤的周边，银增强显示小血管中的金，并在肿瘤细胞周围的细胞外间隙中局部超出血管边界。在肿瘤细胞质内未观察到金颗粒。在肿瘤边缘，通过电子显微镜在单核吞噬细胞系统的细胞中偶尔看到非增强的金。我们通过使用替代的含水量标记物，罗丹明B异硫氰酸盐-葡聚糖，获得了与银增强相同的定位模式。我们的结论是，脂质体的特定组合物，它有能力保持在循环中的半衰期为12-24小时，也能够横向的小血管，包括那些在肿瘤的内皮细胞，并外渗到细胞外的空间。（400字处删节）
Using light and electron microscopy, we investigated the in vivo distribution of liposomes sterically stabilized by specific lipids which prolong their circulation in blood. Tissue distribution of sterically stabilized liposomes composed of distearoyl phosphatidylcholine:cholesterol:monosialoganglioside GM1 (10:5:1)-encapsulated 67Ga-Desferal indicates that more than 30% of liposomes still remain in the blood at 24 h after tail vein injection. Moreover, such liposomes accumulated in tumors (C-26 colon carcinoma cells implanted s.c.), reaching almost the same level of uptake as liver (approximately 20% injected dose/g tissue). The microscopic localization of liposomes labeled with encapsulated colloidal gold or rhodamine-labeled dextran coincided well with the tissue distribution. To evaluate circulation parameters, two sizes of gold-containing egg phosphatidylcholine:cholesterol:distearoyl phosphatidylethanolamine (derivatized at its amino position with a 1900 molecular weight segment of polyethylene glycol) (10:5:0.8) liposomes were injected. The plasma was examined by electron microscopy of negative-stained preparations at 0.5, 4, and 24 h after liposome injection. It was found that the ratio of small (less than 100 nm diameter) to large (greater than 100 nm) liposomes increased with time, indicating a much faster clearance of the larger liposomes. To detect the localization of liposomes in various tissues, appropriate samples were fixed 24 h after the injection of gold-containing liposomes (between 80 and 100 nm in diameter) composed of egg phosphatidylcholine:cholesterol:monosialoganglioside GM1 (10:5:1) or egg phosphatidylcholine:cholesterol:derivatized distearoyl phosphatidylethanolamine. The tissues examined for this study included normal liver, bone marrow, and implanted neoplasms. Silver-enhanced colloidal gold was found predominantly within Kupffer cells in the normal liver and within macrophages in the bone marrow. Rarely were any silver-enhanced gold particles detected in hepatocytes. In all preparations, electron microscopy revealed the presence of gold in endosomes and lysosomes of fixed sinusoidal lining macrophages in the liver and bone marrow. Peripheral to the implanted tumors, silver enhancement revealed gold in small blood vessels and focally beyond the vessel boundaries in extracellular spaces around tumor cells. Gold particles were not observed within the tumor cell cytoplasm. At the tumor border, nonenhanced gold was occasionally seen by electron microscopy in cells of the mononuclear phagocyte system. We obtained the same localization pattern as with silver enhancement by using an alternative aqueous content marker, rhodamine B isothiocyanate-dextran. We conclude that liposomes of specific composition, which have the ability to remain in circulation with a half-life of 12-24 h, are also able to transverse the endothelium of small blood vessels, including those in tumors, and extravasate into extracellular spaces.(ABSTRACT TRUNCATED AT 400 WORDS)