Polymeric micelles modified by folate-PEG-lipid for targeted drug delivery to cancer cells in vitro
Polymeric micelles modified by folate-PEG-lipid for targeted drug delivery to cancer cells in vitro
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DOI：
10.1166/jnn.2008.093
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发表时间：
2008-06-01
影响因子：
--
通讯作者：
Maitani, Yoshie
中科院分区：
文献类型：
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作者：
Hayama, Akihiro;Yamamoto, Tatsuhiro;Maitani, Yoshie
一种新的技术开发的配体靶向聚合物胶束，可适用于各种配体的形成。为实现肿瘤靶向给药，将喜树碱（CPT）聚合物胶束经叶酸修饰，制备叶酸受体靶向药物载体。在制备载药聚合物胶束时加入叶酸连接的PEG（5000）-二硬脂酰磷脂酰乙醇胺（folate-PEG（5000）-DSPE），导致叶酸配体暴露于表面。叶酸修饰的CPT-负载的聚合物胶束（F-胶束）进行了评估，通过测量细胞摄取使用流式细胞仪，荧光显微镜，共聚焦激光扫描显微镜，并通过细胞毒性测量。结果表明，F-胶束在高表达叶酸受体（FR）的KB细胞中显示出更高的细胞摄取，在KB细胞中显示出比非叶酸修饰的CPT聚合物胶束（普通胶束）更高的细胞毒性，但在FR阴性的HepG 2细胞中则没有。这一结果表明，聚合物胶束成功地修饰叶酸连接的脂质。
A novel technique was developed for the formation of ligand-targeted polymeric micelles that can be applicable to various ligands. For tumor-specific drug delivery, camptothecin (CPT)-loaded polymeric micelles were modified by folate to produce a folate-receptor-targeted drug carrier. Folate-linked PEG(5000)-distearoylphosphatidylethanolamine (folate-PEG(5000)-DSPE) was added when preparations of drug-loaded polymeric micelles, resulting in folate ligands exposed to the surface. Folate-modified CPT-loaded polymeric micelles (F-micelle) were evaluated by measuring cellular uptake using a flow cytometer, fluorescence microscopy, and confocal laser scanning microscopy, and by cytotoxicity measurement. The results revealed that F-micelle showed higher cellular uptake in KB cells over-expressing folate receptor (FR) and higher cytotoxicity compared with non-folate modified CPT-loaded polymeric micelles (plain micelles) in KB cells, but not in FR-negative HepG2 cells. This result indicated that polymeric micelles were successfully modified by the folate-linked lipid.