Synthesis of Water-Soluble Imidazolium Polyesters as Potential Nonviral Gene Delivery Vehicles

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• 作者：Ashley M. Nelson ; Allison M. Pekkanen ; Neil L. Forsythe ; John H. Herlihy ; Musan Zhang ; Timothy E. Long
• 刊名：Biomacromolecules
• 出版年：2017
• 出版时间：January 9, 2017
• 年：2017
• 卷：18
• 期：1
• 页码：68-76
• 全文大小：559K
• ISSN：1526-4602

文摘

The inherent hydrolytic reactivity of polyesters renders them excellent candidates for a variety of biomedical applications. Incorporating ionic groups further expands their potential impact, encompassing charge-dependent function such as deoxyribonucleic acid (DNA) binding, antibacterial properties, and pH-responsiveness. Catalyst-free and solvent-free polycondensation of a bromomethyl imidazolium-containing (BrMeIm) diol with neopentylglycol (NPG) and adipic acid (AA) afforded novel charged copolyesters with pendant imidazolium sites. Varying ionic content influenced thermal properties and offered a wide-range, −41 to 40 °C, of composition-dependent glass transition temperatures (T_gs). In addition to desirable melt and thermal stability, polyesters with ionic concentrations ≥15 mol % readily dispersed in water, suggesting potential as nonviral gene delivery vectors. An electrophoretic gel shift assay confirmed the novel cationic copolyesters successfully bound DNA at an N/P ratio of 4 for 50 mol % and 75 mol % charged copolyesters (P(NA₅₀-co-ImA₅₀) and P(NA₂₅-co-ImA₇₅)), and an N/P ratio of 5 for 100 mol % Im (PImA). Polyplexes exhibited insignificant cytotoxicity even at high concentrations (200 μg/mL), and a Luciferase transfection assay revealed the ionic (co)polyesters transfected DNA significantly better than the untreated controls. The successful transfection of these novel (co)polyesters inspires future imidazolium-containing polyester design.