School of Chemical and Process Engineering, University of Leeds, Leeds LS2 9JT, United Kingdom.
School of Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
Biomacromolecules. 2022 Jun 13;23(6):2362-2373. doi: 10.1021/acs.biomac.2c00136. Epub 2022 May 12.
Interaction between the anionic phosphodiester backbone of DNA/RNA and polycations can be exploited as a means of delivering genetic material for therapeutic and agrochemical applications. In this work, quaternized poly(2-(dimethylamino)ethyl methacrylate)--poly(,-dimethylacrylamide) (PQDMAEMA--PDMA) double hydrophilic block copolymers (DHBCs) were synthesized reversible addition-fragmentation chain-transfer (RAFT) polymerization as nonviral delivery vehicles for double-stranded RNA. The assembly of DHBCs and dsRNA forms distinct polyplexes that were thoroughly characterized to establish a relationship between the length of the uncharged poly(-dimethylacrylamide) (PDMA) block and the polyplex size, complexation efficiency, and colloidal stability. Dynamic light scattering reveals the formation of smaller polyplexes with increasing PDMA lengths, while gel electrophoresis confirms that these polyplexes require higher N/P ratio for full complexation. DHBC polyplexes exhibit enhanced stability in low ionic strength environments in comparison to homopolymer-based polyplexes. enzymatic degradation assays demonstrate that both homopolymer and DHBC polymers efficiently protect dsRNA from degradation by RNase A enzyme.
DNA/RNA 的阴离子磷酸二酯骨架与聚阳离子之间的相互作用可被利用来作为递送遗传物质的方法，用于治疗和农用化学品应用。在这项工作中，通过可逆加成-断裂链转移（RAFT）聚合合成了季铵化聚（2-（二甲氨基）乙基甲基丙烯酸酯）-聚（-二甲基丙烯酰胺）（PQDMAEMA-PDMA）两亲性嵌段共聚物（DHBC），用作双链 RNA 的非病毒递送载体。DHBC 和 dsRNA 的组装形成了不同的聚集体，对其进行了全面的表征，以建立无电荷聚（-二甲基丙烯酰胺）（PDMA）嵌段长度与聚集体大小、络合效率和胶体稳定性之间的关系。动态光散射显示，随着 PDMA 长度的增加，形成更小的聚集体，而凝胶电泳证实这些聚集体需要更高的 N/P 比才能完全络合。与基于均聚物的聚集体相比，DHBC 聚集体在低离子强度环境中表现出增强的稳定性。酶降解实验表明，均聚物和 DHBC 聚合物都能有效地保护 dsRNA 免受 RNase A 酶的降解。
