Selective delivery of folate-PEG-linked, nanoemulsion-loaded aclacinomycin A to KB nasopharyngeal cells and xenograft: Effect of chain length and amount of folate-PEG linker
Selective delivery of folate-PEG-linked, nanoemulsion-loaded aclacinomycin A to KB nasopharyngeal cells and xenograft: Effect of chain length and amount of folate-PEG linker
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DOI：
10.1080/10611860802201464
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发表时间：
2008-01-01
影响因子：
4.5
通讯作者：
Maitani, Yoshie
中科院分区：
文献类型：
--
作者：
Ohguchi, Yukino;Kawano, Kumi;Maitani, Yoshie
为了研究叶酸靶向纳米乳剂负载阿克拉霉素A（ACM）对叶酸受体（FR）阳性细胞的使用，我们试图通过修改叶酸-PEG连接体的链长和量来优化纳米乳剂的靶向能力。将叶酸连接的纳米乳液负载的ACM与0.24摩尔%的叶酸-聚（乙二醇）3400-（叶酸-PEG 3400-）和叶酸-PEG 5000-二硬脂酰磷脂酰乙醇胺（DSPE）以及0.03摩尔%的叶酸-PEG 5000-DSPE配制成纳米乳液。在过表达FR的人鼻咽肿瘤细胞系KB中实现了选择性FR介导的摄取，但在人肝母细胞瘤细胞系（FR（-））HepG 2中未实现。在相同量的叶酸修饰下，随着PEG链长度的增加，与KB细胞的缔合增加。0.03mol%和0.24mol%叶酸-PEG 5000连接的纳米乳与细胞的结合分别是非叶酸纳米乳的5倍和3.3倍，而它们的细胞毒性相似。在肿瘤接种后第24天，静脉注射0.03和0.24mol%叶酸-PEG 5000连接的纳米乳剂和非叶酸纳米乳剂均比ACM溶液更显著地抑制肿瘤生长（p <0.01）。这项研究表明，叶酸连接的纳米乳液是可行的肿瘤靶向ACM交付，叶酸修饰与足够长的PEG链和少量的纳米乳液是一种有效的方式，将纳米乳液靶向肿瘤细胞。
To investigate the use of folate-targeted nanoemulsion-loaded aclacinomycin A (ACM) to folate receptor (FR)-positive cells, we attempted to optimize the targeting ability of nanoemulsions by modifying the chain length and amount of the folate-PEG linker. Folate-linked, nanoemulsion-loaded ACM were formulated with 0.24mol% of folate-poly (ethylene glycol)3400- (folate-PEG3400-) and folate-PEG5000-distearoylphosphatidylethanolamine (DSPE), and 0.03mol% of folate-PEG5000-DSPE in nanoemulsions. Selective FR-mediated uptake was achieved in a human nasopharyngeal tumor cell line, KB, which overexpresses FR, but not in a human hepatoblastoma cell line, (FR(-)) HepG2. At the same amount of folate modification, the association with KB cells was increased with increasing the PEG-chain length. The association of 0.03and 0.24mol% folate-PEG5000-linked nanoemulsions with cells was 5- and 3.3-fold higher than that of non-folate nanoemulsion, respectively, while their cytotoxicity was similar. Both 0.03 and 0.24mol% folate-PEG5000-linked nanoemulsions and non-folate nanoemulsion following intravenous injection inhibited tumor growth more significantly than ACM solution on day 24 following tumor inoculation (p0.01). This study demonstrates that a folate-linked nanoemulsion is feasible for tumor-targeted ACM delivery, and that folate modification with a sufficiently long PEG-chain and a small amount of nanoemulsion is an effective way of targeting nanoemulsion to tumor cells.