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首页> 外文期刊>Journal of drug targeting >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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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.

机译：叶酸-PEG连接的纳米乳剂负载阿克拉霉素A向KB鼻咽细胞和异种移植的选择性递送：链长和叶酸-PEG连接体数量的影响。

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摘要

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 0.24 mol% of folate-poly (ethylene glycol)(3400)- (folate-PEG(3400)-) and folate-PEG(5000)-distearoylphosphatidylethanolamine (DSPE), and 0.03 mol% of folate-PEG(5000)-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 0.03 and 0.24 mol% folate-PEG(5000)-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 0.24 mol% folate-PEG(5000)-linked nanoemulsions and non-folate nanoemulsion following intravenous injection inhibited tumor growth more significantly than ACM solution on day 24 following tumor inoculation (p < 0.01). 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.
机译：若要研究叶酸靶向的纳米乳液负载阿克拉霉素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接头的链长和数量来优化纳米乳液的靶向能力。用0.24 mol％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）配制叶酸连接的负载纳米乳液的ACM纳米乳液中叶酸-PEG（5000）-DSPE的摩尔％。选择性FR介导的摄取是在人类鼻咽肿瘤细胞系KB中实现的，该细胞系过表达FR，但在人类肝母细胞瘤细胞系（FR（-））HepG2中却没有。在相同的叶酸修饰量下，与KB细胞的缔合随着PEG链长度的增加而增加。 0.03和0.24 mol％的叶酸-PEG（5000）连接的纳米乳剂与细胞的缔合分别比非叶酸的纳米乳剂高5到3.3倍，而它们的细胞毒性相似。静脉注射后0.03和0.24 mol％的叶酸-PEG（5000）连接的纳米乳剂和非叶酸的纳米乳剂在肿瘤接种后第24天比ACM溶液对肿瘤的生长抑制作用更为显着（p <0.01）。这项研究表明，叶酸连接的纳米乳液可用于靶向肿瘤的ACM递送，而叶酸修饰具有足够长的PEG链和少量的纳米乳液是将纳米乳液靶向肿瘤细胞的有效方法。

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