Non-covalent complexes of folic acid and oleic acid conjugated polyethylenimine: An efficient vehicle for antisense oligonucleotide delivery.
Non-covalent complexes of folic acid and oleic acid conjugated polyethylenimine: An efficient vehicle for antisense oligonucleotide delivery.
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DOI：
10.1016/j.colsurfb.2015.07.047
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发表时间：
2015-11-01
期刊：
影响因子：
--
通讯作者：
Teng L
中科院分区：
文献类型：
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作者：
Yang S;Yang X;Liu Y;Zheng B;Meng L;Lee RJ;Xie J;Teng L
聚乙烯亚胺（PEI）共轭油酸（PEI-OA）和评估作为LOR-2501，对核糖核苷酸还原酶R1亚基的反义寡核苷酸的递送剂。进一步用叶酸包被PEI-OA/LOR-2501复合物（FA/PEI-OA/LOR-2501）并在肿瘤细胞中进行评价。FA/PEI-OA/LOR-2501的细胞摄取水平是PEI/LOR-2501复合物的两倍以上，并且不受细胞表面上叶酸受体（FR）表达水平的影响。在几种细胞系中观察到有效递送。此外，途径特异性细胞内化抑制剂和标记物用于揭示细胞摄取的主要机制。FA/PEI-OA/LOR-2501显著下调R1 mRNA和R1蛋白表达。FA/PEI-OA的这种新型制剂提供了一种可靠且高效的寡核苷酸递送方法，值得进一步研究。
Polyethylenimine (PEI) was conjugated to oleic acid (PEI-OA) and evaluated as a delivery agent for LOR-2501, an antisense oligonucleotide against ribonucleotide reductase R1 subunit. PEI-OA/LOR-2501 complexes were further coated with folic acid (FA/PEI-OA/LOR-2501) and evaluated in tumor cells. The level of cellular uptake of FA/PEI-OA/LOR-2501 was more than double that of PEI/LOR-2501 complexes, and was not affected by the expression level of folate receptor (FR) on the cell surface. Efficient delivery was seen in several cell lines. Furthermore, pathway specific cellular internalization inhibitors and markers were used to reveal the principal mechanism of cellular uptake. FA/PEI-OA/LOR-2501 significantly induced the downregulation of R1 mRNA and R1 protein. This novel formulation of FA/PEI-OA provides a reliable and highly efficient method for delivery of oligonucleotide and warrants further investigation.