Torchilin V P, Klibanov A L, Huang L, O'Donnell S, Nossiff N D, Khaw B A
Department of Nuclear Medicine, Massachusetts General Hospital, East, Charlestown 02129.
FASEB J. 1992 Jun;6(9):2716-9. doi: 10.1096/fasebj.6.9.1612296.
The less than optimal accumulation of immunoliposome-associated reagents at target sites has often been attributed to the rapid in vivo clearance of immunoliposomes from the blood. In an attempt to overcome the drawback of rapid clearance and use the targeting potential of immunoliposomes, we have prepared long-circulating, 111In-labeled immunoliposomes. Targeting properties and enhanced circulation times were demonstrated in a rabbit model of acute experimental myocardial infarct. The specificity of liposomes for newly exposed intracellular cardiac myosin at the necrotic sites was achieved by incorporating monoclonal antimyosin antibody. Extended circulation times were achieved by cocoating the antimyosin-liposomes with polyethylene glycol (PEG). The half-life of the immunoliposomes was 40 min, which increased to 200 min with 4% mol PEG and to approximately 1000 min with 10% mol PEG. The degree of binding of modified immunoliposomes at the target sites was also dependent on the concentration of PEG incorporated at the liposome surface. This study demonstrates the accumulation of long-circulating targeted liposomes at the area of acute rabbit experimental myocardial infarction.
免疫脂质体相关试剂在靶位点的积累未达最佳水平，这通常归因于免疫脂质体在血液中迅速被体内清除。为克服快速清除这一缺点并利用免疫脂质体的靶向潜力，我们制备了长循环、¹¹¹In标记的免疫脂质体。在急性实验性心肌梗死的兔模型中证明了其靶向特性和延长的循环时间。通过掺入单克隆抗肌球蛋白抗体，脂质体对坏死部位新暴露的细胞内心肌肌球蛋白具有特异性。通过用聚乙二醇（PEG）共包被抗肌球蛋白脂质体实现了延长的循环时间。免疫脂质体的半衰期为40分钟，在4%摩尔PEG时增加到200分钟，在10%摩尔PEG时增加到约1000分钟。修饰的免疫脂质体在靶位点的结合程度也取决于脂质体表面掺入的PEG浓度。本研究证明了长循环靶向脂质体在急性兔实验性心肌梗死区域的积累。
