Influence of Oligospermines Architecture on Their Suitability for siRNA Delivery

详细信息    查看全文

• 作者：Maha Elsayed ; Vincent Corrand ; Vidula Kolhatkar ; Yuran Xie ; Na Hyung Kim ; Rohit Kolhatkar ; Olivia M. Merkel
• 刊名：Biomacromolecules
• 出版年：2014
• 出版时间：April 14, 2014
• 年：2014
• 卷：15
• 期：4
• 页码：1299-1310
• 全文大小：492K
• 年卷期：v.15,no.4(April 14, 2014)
• ISSN：1526-4602

文摘

Spermines are naturally abundant polyamines that partially condense nucleic acids and exhibit the proton-sponge effect in an acidic environment. However, spermines show a limited efficiency for transfecting nucleic acids because of their low molecular weight. Therefore, spermines need to be modified to be used as nonviral vectors for nucleic acids. Here, we synthesized linear bisspermine as well as a linear and dendritic tetraspermine with different molecular architectures. These oligospermines were self-assembled into polyplexes with siRNA. The structure鈥揳ctivity relationship of the oligospermines was evaluated in terms of their efficiency for delivering siRNA into a nonsmall cell lung carcinoma cell line. Oligospermines displayed minimal cytotoxicity but efficient siRNA condensation and showed better stability against polyanions than polyethylenimine. The morphology of the polyplexes was strongly affected by the oligospermine architecture. Linear tetraspermine/siRNA polyplexes showed the best gene-silencing efficiency among the oligospermines tested at both the mRNA and protein expression levels, indicating the most favorable structure for siRNA delivery.