Department of Materials Science and Engineering, Faculty of Engineering, Monash University, Clayton, Victoria 3800, Australia.
Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
ACS Appl Mater Interfaces. 2020 Oct 7;12(40):44485-44498. doi: 10.1021/acsami.0c13309. Epub 2020 Sep 28.
Treatment of multidrug-resistant (MDR) bacterial infections increasingly relies on last-line antibiotics, such as polymyxins, with the urgent need for discovery of new antimicrobials. Nanotechnology-based antimicrobials have gained significant importance to prevent the catastrophic emergence of MDR over the past decade. In this study, phytantriol-based nanoparticles, named cubosomes, were prepared and examined by minimum inhibitory concentration (MIC) and time-kill assays against Gram-negative bacteria: , , and . Phytantriol-based cubosomes were highly bactericidal against polymyxin-resistant, lipopolysaccharide (LPS)-deficient strains. Small-angle neutron scattering (SANS) was employed to understand the structural changes in biomimetic membranes that replicate the composition of these LPS-deficient strains upon treatment with cubosomes. Additionally, to further understand the membrane-cubosome interface, neutron reflectivity (NR) was used to investigate the interaction of cubosomes with model bacterial membranes on a solid support. These results reveal that cubosomes might be a new strategy for combating LPS-deficient Gram-negative pathogens.
治疗多重耐药（MDR）细菌感染越来越依赖于最后一线抗生素，如多粘菌素，因此迫切需要发现新的抗菌药物。在过去十年中，基于纳米技术的抗菌药物对于防止 MDR 的灾难性出现变得非常重要。在这项研究中，制备了基于植烷三醇的纳米颗粒，命名为立方脂质体，并通过最低抑菌浓度（MIC）和时间杀伤试验对革兰氏阴性菌： 、 、 进行了检查。基于植烷三醇的立方脂质体对多粘菌素耐药、脂多糖（LPS）缺乏的 菌株具有高度杀菌作用。小角中子散射（SANS）用于了解仿生膜的结构变化，这些仿生膜复制了 LPS 缺乏菌株在立方脂质体处理后的组成。此外，为了进一步了解膜-立方脂质体界面，使用中子反射率（NR）研究了立方脂质体与固体支持上的模型细菌膜的相互作用。这些结果表明，立方脂质体可能是对抗 LPS 缺乏的革兰氏阴性病原体的一种新策略。
