Deng Xiaojian, Zheng Nan, Song Ziyuan, Yin Lichen, Cheng Jianjun
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
Department of Materials Science and Engineering, University of Illinois at Urbana-Champaign, 1304 W Green Street, Urbana, IL 61801, USA.
Biomaterials. 2014 Jun;35(18):5006-15. doi: 10.1016/j.biomaterials.2014.03.005. Epub 2014 Mar 24.
Poly(β-amino ester)s (PBAEs) represent an important class of cationic gene delivery materials which, however, suffer from uncontrolled DNA release due in part to the slow degradation of their polyester backbone. Additionally, PBAEs with high molecular weight (MW) also show considerable toxicities. In this study, we designed and developed PBAEs with trigger-responsive domains built-in polymer backbones that can be rapidly cleaved upon external UV light triggering to promote intracellular DNA release as well as reduce material toxicity. Photo-responsive PBAEs were prepared via polyaddition of (2-nitro-1,3-phenylene)bis(methylene) diacrylate and a bifunctional amine. The nitrobenzene moiety was placed in each repeating unit of the PBAE to allow fast response to external UV irradiation, and thus the ester linkers were cleaved and the polymers were degraded within several minutes upon UV irradiation. Cationic PBAEs with high MWs were able to mediate effective intracellular gene delivery, while upon UV irradiation post-transfection, enhanced DNA unpackaging and reduced material toxicity were observed, which collectively contributed to greatly improved transfection efficiencies in various mammalian cell types tested. This strategy allows precise manipulation of material toxicity and gene release profiles of PBAEs, and thus provides an effective design approach to address critical issues in non-viral gene delivery.
聚（β-氨基酯）（PBAEs）是一类重要的阳离子基因递送材料，然而，由于其聚酯主链降解缓慢，导致DNA释放不受控制。此外，高分子量（MW）的PBAEs也表现出相当大的毒性。在本研究中，我们设计并开发了在聚合物主链中内置触发响应域的PBAEs，其可在外部紫外线触发时快速裂解，以促进细胞内DNA释放并降低材料毒性。通过（2-硝基-1,3-亚苯基）双（亚甲基）二丙烯酸酯与双功能胺的加成聚合反应制备了光响应性PBAEs。将硝基苯部分置于PBAE的每个重复单元中，以便对外部紫外线照射做出快速响应，因此在紫外线照射后几分钟内，酯连接键被裂解，聚合物降解。高分子量的阳离子PBAEs能够介导有效的细胞内基因递送，而在转染后进行紫外线照射时，观察到DNA解包增强且材料毒性降低，这共同导致在各种测试的哺乳动物细胞类型中转染效率大大提高。该策略允许精确控制PBAEs的材料毒性和基因释放概况，从而为解决非病毒基因递送中的关键问题提供了一种有效的设计方法。
