Low Molecular Weight Oligomers with Aromatic Backbone as Efficient Nonviral Gene Vectors

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• 作者：Chao-Ran Luan ; Yan-Hong Liu ; Ji Zhang ; Qing-Ying Yu ; Zheng Huang ; Bing Wang ; Xiao-Qi Yu
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：May 4, 2016
• 年：2016
• 卷：8
• 期：17
• 页码：10743-10751
• 全文大小：786K
• 年卷期：0
• ISSN：1944-8252

文摘

A series of oligomers were synthesized via ring-opening polymerization. Although the molecular weights of these oligomers are only ∼2.5 kDa, they could efficiently bind and condense DNA into nanoparticles. These oligomers gave comparable transfection efficiency (TE) to PEI 25 kDa, while their TE could even increase with the presence of serum, and up to 65 times higher TE than PEI was obtained. The excellent serum tolerance was also confirmed by TEM, flow cytometry, and BSA adsorption assay. Moreover, structure–activity relationship studies revealed some interesting factors. First, oligomers containing aromatic rings in the backbone showed better DNA binding ability. These materials could bring more DNA cargo into the cells, leading to much better TE. Second, the isomerism of the disubstituted phenyl group on the oligomer backbone has large effect on the transfection. The ortho-disubstituted ones gave at least 1 order of magnitude higher TE than meta- or para-disubstituted oligomers. Gel electrophoresis involving DNase and heparin indicated that the difficulty to release DNA might contribute to the lower TE of the latter. Such clues may help us to design novel nonviral gene vectors with high efficiency and biocompatibility.