叶酸受体靶向脂质囊泡中配制的寡核苷酸的高效细胞内递送。

Efficient intracellular delivery of oligonucleotides formulated in folate receptor-targeted lipid vesicles.

作者信息

Zhou Wen, Yuan Xing, Wilson Annette, Yang Lijuan, Mokotoff Michael, Pitt Bruce, Li Song

机构信息

Center for Pharmacogenetics and Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, USA.

出版信息

Bioconjug Chem. 2002 Nov-Dec;13(6):1220-5. doi: 10.1021/bc025569z.

DOI:10.1021/bc025569z

PMID:12440856

Abstract

In this study, a novel lipid vector has been developed for targeted delivery of oligodeoxynucleotides (ODN) to tumors that overexpress folate receptor. This is based on a method developed by Semple et al. (1), which utilizes an ionizable aminolipid (1,2-dioleoyl-3-(dimethylammonio)propane, DODAP) and an ethanol-containing buffer system for encapsulating large quantities of polyanionic ODN in lipid vesicles. Folate is incorporated into the lipid vesicles via a distearoylphosphatidylethanolamine-poly(ethylene glycol) (DSPE-PEG) spacer. These vesicles are around 100-200 nm in diameter with an ODN entrapment efficiency of 60-80%. Folate mediated efficient delivery of ODN to KB cells that overexpress folate receptor. Uptake of folate-targeted lipidic ODN by KB cells is about 8-10-fold more efficient than that of lipidic ODN without a ligand or free ODN. This formulation is resistant to serum. Thus, targeted delivery of ODN via this novel lipid vector may have potential in treating tumors that overexpress folate receptors.

摘要

在本研究中，已开发出一种新型脂质载体，用于将寡脱氧核苷酸（ODN）靶向递送至过表达叶酸受体的肿瘤细胞。这是基于Semple等人开发的一种方法（1），该方法利用可电离的氨基脂质（1,2-二油酰基-3-（二甲基铵）丙烷，DODAP）和含乙醇的缓冲系统，将大量聚阴离子ODN封装在脂质囊泡中。叶酸通过二硬脂酰磷脂酰乙醇胺-聚（乙二醇）（DSPE-PEG）间隔物掺入脂质囊泡中。这些囊泡直径约为100-200nm，ODN包封效率为60-80%。叶酸介导ODN高效递送至过表达叶酸受体的KB细胞。KB细胞对叶酸靶向脂质ODN的摄取效率比无配体的脂质ODN或游离ODN高约8-10倍。该制剂对血清具有抗性。因此，通过这种新型脂质载体靶向递送ODN在治疗过表达叶酸受体的肿瘤方面可能具有潜力。