State Key Laboratory of Heavy Oil Processing and Centre for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao, Shandong 266555, China.
Biomaterials. 2012 Jan;33(2):592-603. doi: 10.1016/j.biomaterials.2011.09.059. Epub 2011 Oct 8.
Biomimicry of antimicrobial peptides secreted by innate immune systems represents a major strategy in developing novel antibacterial treatments. There are however emerging concerns over the possible compromise of host natural defenses by these biomimetic peptides due to their structural similarity. In our recent work we have extended the search by exploring the potential from unnatural synthetic antimicrobial peptides. Here we show that a series of surfactant-like peptides (A(m)K(n), m ≥ 3, n = 1, 2) can kill not only bacteria but also cancerous HeLa cells in similar manner. Under the same experimental conditions, however, these peptides showed little affinity to NIH 3T3 cells and human red blood cells (hRBCs), thus demonstrating high biocompatibility in selective responses to host mammalian cells and low hemolysis. A(9)K(1) was most effective in killing HeLa cells, a trend consistent with their bactericidal effects against Escherichia coli and Bacillus subtilis. Mechanistic investigations through combined studies of SEM and fluorescence assays revealed that the killing of bacteria and cancerous cells was caused by disrupting cell membranes, initiated by electrostatic interactions between cationic peptides and negatively charged cell membranes. In contrast, the absence of such interactions in the case of NIH 3T3 and hRBCs over the same peptide concentration range rendered low cytotoxicity. The most effective killing power of A(9)K(1) within this series benefited from the combined effects of several factors including modest micellar concentration and balanced amphiphilicity, consistent with its propensity of self-assembly and effective membrane lytic power.
天然免疫系统分泌的抗菌肽的仿生学代表了开发新型抗菌治疗方法的主要策略。然而，由于这些仿生肽的结构相似，人们对它们可能破坏宿主天然防御机制的问题越来越关注。在我们最近的工作中，我们通过探索非天然合成抗菌肽的潜力扩展了搜索范围。在这里，我们展示了一系列表面活性剂样肽（A(m)K(n)，m ≥ 3，n = 1，2）不仅可以杀死细菌，还可以以类似的方式杀死癌细胞 HeLa。然而，在相同的实验条件下，这些肽对 NIH 3T3 细胞和人红细胞（hRBC）几乎没有亲和力，因此在选择性响应宿主哺乳动物细胞和低溶血方面表现出高生物相容性。A(9)K(1)在杀死 HeLa 细胞方面最为有效，这一趋势与它们对大肠杆菌和枯草芽孢杆菌的杀菌作用一致。通过 SEM 和荧光分析联合研究的机制研究表明，细菌和癌细胞的死亡是由阳离子肽与带负电荷的细胞膜之间的静电相互作用引发的细胞膜破坏引起的。相比之下，在相同的肽浓度范围内，NIH 3T3 和 hRBC 中不存在这种相互作用，导致细胞毒性低。在这个系列中，A(9)K(1)的最有效杀伤能力得益于包括适度胶束浓度和平衡的两亲性在内的多种因素的综合作用，这与其自组装倾向和有效的膜裂解能力一致。
