Sequence Control as a Powerful Tool for Improving the Selectivity of Antimicrobial Polymers
Sequence Control as a Powerful Tool for Improving the Selectivity of Antimicrobial Polymers
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DOI：
10.1021/acsami.7b14996
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发表时间：
2017-11-22
影响因子：
9.5
通讯作者：
Perrier, Sebastien
中科院分区：
文献类型：
--
作者：
Kuroki, Agnes;Sangwan, Parveen;Perrier, Sebastien
抗菌聚合物似乎是解决当前细菌对传统抗生素耐药性发展的有前途的替代品，因为它们依赖于细菌膜破坏。本研究研究了抗菌聚合物上疏水性和阳离子官能团的分段对其在细菌和哺乳动物细胞之间的选择性的影响。使用 RAFT 技术，以受控方式合成统计、二嵌段和高度分段的多嵌段共聚物。通过 HPLC 分析聚合物，发现分段对其整体疏水性有显着影响。此外，改变掺入的阳离子共聚单体的量以产生小的生物活性大分子库。研究了这些化合物对病原菌（大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌和表皮葡萄球菌）的抗菌特性，并使用溶血和红细胞聚集测定以及哺乳动物细胞活力测定测试了它们的生物相容性。在所有情况下，发现二嵌段和多嵌段共聚物优于统计共聚物，并且对于阳离子共聚单体含量低的聚合物，与统计和二嵌段类似物相比，多嵌段对铜绿假单胞菌和表皮葡萄球菌的选择性显着增加。这项工作强调了分割对材料的物理特性及其与生物系统的相互作用的显着影响。由于多嵌段共聚物对某些细菌菌株具有出色的选择性，所提出的材料是治疗感染的有前途的平台和对抗抗菌素耐药性的宝贵工具。
Antimicrobial polymers appear as a promising alternative to tackle the current development of bacterial resistance against conventional antibiotics as they rely on bacterial membrane disruption. This study investigates the effect of segmentation of hydrophobic and cationic functionalities on antimicrobial polymers over their selectivity between bacteria and mammalian cells. Using RAFT technology, statistical, diblock, and highly segmented multiblock copolymers were synthesized in a controlled manner. Polymers were analyzed by HPLC, and the segmentation was found to have a significant influence on their overall hydrophobicity. In addition, the amount of incorporated cationic comonomer was varied to yield a small library of bioactive macromolecules. The antimicrobial properties of these compounds were probed against pathogenic bacteria (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus epidermidis), and their biocompatibility was tested using hemolysis and erythrocyte aggregation assays, as well as mammalian cell viability assays. In all cases, diblock and multiblock copolymers were found to outperform statistical copolymers, and for polymers with a low content of cationic comonomer, the multiblock showed a tremendously increased selectivity for P. aeruginosa and S. epidermidis compared to its statistical and diblock analogue. This work highlights the remarkable effect of segmentation on both the physical properties of the materials as well as their interaction with biological systems. Due to the outstanding selectivity of multiblock copolymers toward certain bacteria strains, the presented materials are a promising platform for the treatment of infections and a valuable tool to combat antimicrobial resistance.