Immunotargeting of liposomes containing lipophilic antitumor prodrugs.
Immunotargeting of liposomes containing lipophilic antitumor prodrugs.
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含有亲脂性抗肿瘤前药的脂质体的免疫靶向。
DOI：
10.1023/a:1018933632318
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发表时间：
1993
影响因子：
3.7
通讯作者：
Huang,L
中科院分区：
文献类型：
--
作者：
Mori,A;Kennel,SJ;Huang,L
最近开发的脂质体的潜在的治疗应用与降低的亲和力的网状内皮系统和延长的循环时间作为亲脂性前药的靶向系统进行了检查。在这些研究中，使用了由磷脂酰胆碱和胆固醇组成的脂质体，还含有单唾液酸神经节苷脂（GM 1）或与磷脂酰乙醇胺（PEG-PE）缀合的聚乙二醇。以三种亲脂性抗肿瘤前药：N-三氟乙酰阿霉素-14-戊酸酯（AD 32）、araC-二磷酸甘油二酯（araCdPdG）和3′，5 ′-o-二棕榈酰-5-氟-2 ′-脱氧尿苷（dpFUdR）为研究对象，考察了亲脂性前药掺入长循环脂质体和免疫脂质体后对其在小鼠体内分布的影响。用含有亲脂性前药的无抗体脂质体进行的生物分布研究表明，在药物/脂质摩尔比为3：97的三种亲脂性前药中的每一种存在下，GM 1或PEG 2000-PE在延长脂质体循环时间方面的活性似乎得到保留。然后使用小鼠模型检查亲脂性前药掺入对免疫脂质体的靶结合的影响。将AD 32或dpFUdR掺入免疫脂质体中，导向正常内皮，不影响免疫脂质体的靶向性，表明这些含亲脂性前药的免疫脂质体在治疗肺肿瘤中的潜在有效性。相反，araCdPdG的掺入导致免疫脂质体的靶结合通过尚不清楚的机制显著降低。
Potential therapeutic applications of recently developed liposomes with a reduced affinity to the reticuloendothelial systems and a prolonged circulation time as targeting systems for lipophilic prodrugs were examined. In these studies, liposomes composed of phosphatidylcholine and cholesterol, additionally containing monosialoganglioside (GM1) or polyethylene glycol conjugated to phosphatidyl-ethanolamine (PEG-PE), were used. Three antitumor lipophilic prodrugs,N-trifluoroacetyl-adriamycin-14-valerate (AD32), araC-diphosphate-diglyceride (araCdPdG), and 3′,5′-o-dipalmitoyl-5-fluoro-2′-deoxyuridine (dpFUdR), were used to examine the effect of lipophilic prodrug incorporation into long-circulating liposomes and immunoliposomes on their biodistribution in mouse. Biodistribution studies with antibody-free liposomes containing lipophilic prodrugs showed that the activities of GM1or PEG2000-PE in prolonging the circulation time of liposomes appeared to be preserved in the presence of each of the three lipophilic prodrugs at a drug/lipid molar ratio of 3:97. The effect of lipophilic prodrug incorporation on target binding of immunoliposomes was then examined using a mouse model. Incorporation of AD32 or dpFUdR into immunoliposomes, directed to the normal endothelium, did not affect the targetability of immunoliposomes, suggesting a potential effectiveness of these lipophilic prodrug-containing immunoliposomes in therapy for lung tumors. On the contrary, incorporation of araCdPdG resulted in significantly reduced target binding of immunoliposomes by yet unknown mechanism(s).
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