Well-defined reducible cationic nanogels based on functionalized low-molecular-weight PGMA for effective pDNA and siRNA delivery
Well-defined reducible cationic nanogels based on functionalized low-molecular-weight PGMA for effective pDNA and siRNA delivery
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DOI：
10.1016/j.actbio.2016.06.006
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发表时间：
2016-09-01
影响因子：
9.7
通讯作者：
Xu, Fu-Jian
中科院分区：
文献类型：
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作者：
Li, Rui-Quan;Wu, Wei;Xu, Fu-Jian
基于核酸的基因疗法是治疗许多疑难杂症的一种有前景的治疗选择。对于非病毒基因载体来说，低分子量聚合载体一般转染性能较差，但有利于其最终从体内清除。最近，据报道，胺化聚甲基丙烯酸缩水甘油酯（PGMA）是一种潜在的基因载体。基于乙二胺（ED）功能化的低分子量PGMA（由PGED表示），本文提出了一种灵活的策略，以设计具有友好交联剂的新型明确的可还原阳离子纳米凝胶（由PGED-NG表示），以实现高效的核酸递送。 α-硫辛酸（LA）是人体内的一种天然抗氧化剂，很容易将其引入ED功能化的PGMA中并交联产生具有大量可还原硫辛酰基的阳离子PGED-NG。 PGED-NGs 可以有效地复合质粒 DNA (pDNA) 和短干扰 RNA (siRNA)。与原始PGED相比，PGED-NG表现出更好的pDNA转染性能。 PGED-NGs还可以有效地将MALATI siRNA（siR-M）转运到肝癌细胞中，并显着抑制癌细胞的增殖和迁移。目前的工作表明，涉及 LA 交联剂的可还原阳离子纳米凝胶是高性能核酸递送系统的一种有竞争力的候选者。
Nucleic acid-based gene therapy is a promising treatment option to cure numerous intractable diseases. For non-viral gene carriers, low-molecular-weight polymeric vectors generally demonstrate poor transfection performance, but benefit their final removals from the body. Recently, it was reported that aminated poly(glycidyl methacrylate) (PGMA) is one potential gene vector. Based on ethylenediamine (ED)-functionalized low-molecular-weight PGMA (denoted by PGED), a flexible strategy was herein proposed to design new well-defined reducible cationic nanogels (denoted by PGED-NGs) with friendly crosslinking reagents for highly efficient nucleic acid delivery. alpha-Lipoic acid (LA), one natural antioxidant in human body, was readily introduced into ED-functionalized PGMA and crosslinked to produce cationic PGED-NGs with plentiful reducible lipoyl groups. PGED-NGs could effectively complex plasmid DNA (pDNA) and short interfering RNA (siRNA). Compared with pristine PGED, PGED-NGs exhibited much better performance of pDNA transfection. PGED-NGs also could efficiently transport MALATI siRNA (siR-M) into hepatoma cells and significantly suppressed the cancer cell proliferation and migration. The present work indicated that reducible cationic nanogels involving LA crosslinking reagents are one kind of competitive candidates for high-performance nucleic acid delivery systems.