School of Life Sciences, Jinlin University, Changchun 130012, China.
School of Life Sciences, Jinlin University, Changchun 130012, China; College of Pharmacy, The Ohio State University, Columbus 43210, USA.
Int J Pharm. 2015 Apr 30;484(1-2):44-50. doi: 10.1016/j.ijpharm.2015.02.036. Epub 2015 Feb 16.
A reduction-sensitive cross-linked polyethylenimine derivative PEI-SS-OA was synthesized and evaluated for oligonucleotide delivery. PEI-SS-OA was shown to condense LOR-2501, an oligonucleotide targeting ribonucleotide reductase R1 subunit (RRM1), into positively charged complexes. The reductive degradation of the PEI-SS-OA induced by dithiothreitol was confirmed by a gel retardation assay. In vitro experiments revealed that the reduction-sensitive PEI-SS-OA was less cytotoxic and more effective in oligonucleotide delivery than the control 25kDa PEI. This study demonstrates that a reducibly degradable cationic polymer PEI-SS-OA possesses both higher oligonucleotide delivery efficiency and lower cytotoxicity than PEI (25 kDa), therefore is an attractive candidate for further in vivo evaluation.
一种还原敏感性的交联聚乙烯亚胺衍生物 PEI-SS-OA 被合成并评估用于寡核苷酸递药。PEI-SS-OA 被证明可以将 LOR-2501 （一种靶向核糖核苷酸还原酶 R1 亚基（RRM1）的寡核苷酸）凝聚成带正电荷的复合物。二硫苏糖醇诱导的 PEI-SS-OA 的还原降解通过凝胶阻滞实验得到证实。体外实验表明，与对照 25kDaPEI 相比，还原敏感的 PEI-SS-OA 的细胞毒性更低，寡核苷酸递送效果更好。本研究表明，可还原降解的阳离子聚合物 PEI-SS-OA 具有比 PEI（25kDa）更高的寡核苷酸递送效率和更低的细胞毒性，因此是进一步体内评价的有吸引力的候选物。
