Division for Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, Zagreb 10000, Croatia.
The Institute of Molecules and Materials of Le Mans, University of Le Mans, Avenue Olivier Messiaen, Le Mans cedex 9, 72085, France.
Colloids Surf B Biointerfaces. 2024 Nov;243:114158. doi: 10.1016/j.colsurfb.2024.114158. Epub 2024 Aug 12.
The rise of the populations of antibiotic resistant bacteria represents an increasing threat to human health. In addition to the synthesis of new antibiotics, which is an extremely expensive and time-consuming process, one of the ways to combat bacterial infections is the use of gold nanoparticles (Au NPs) as the vehicles for targeted delivery of therapeutic drugs. Since such a strategy requires the investigation of the effect of Au NPs (with and without drugs) on both bacterial and human cells, we investigated how the presence of coating-free Au NPs affects the physicochemical properties of lipid membranes that model prokaryotic (PRO) and eukaryotic (EU) cells. PRO/EU systems prepared as multilamellar liposomes (MLVs) and hybrid structures (HSs) from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG)/1,2-dipalmitoyl-sn-glycero-3-phosphoserine (DPPS) in the absence (MLVs)/presence (HSs) of differently distributed Au NPs (sizes ∼20 nm) reported stabilization of the gel phase of PRO systems in comparison with EU one (DSC data of PRO/EU were T(MLVs) ≈ 41.8 °C/42.0 °C, T¯ (HSs) ≈ 43.1 °C/42.4 °C, whereas UV-Vis response T(MLVs) ≈ 41.5 °C/42.0 °C, T¯ (HSs) ≈ 42.9 °C/41.1 °C). Vibrational spectroscopic data unraveled a substantial impact of Au NPs on the non-polar part of lipid bilayers, emphasizing the increase of kink and gauche conformers of the hydrocarbon chain. By interpreting the latter as Au NPs-induced defects, which exert the greatest effect when Au NPs are found exclusively outside the lipid membrane, these findings suggested that Au NPs reduced the compactness of EU-based lipid bilayers much more than in analogous PRO systems. Since the uncoated Au NPs manifested adverse effects when applied as antimicrobials, the results obtained in this work contribute towards recognizing AuNP functionalization as a strategy in tuning and reversing this effect.
抗生素耐药菌数量的增加对人类健康构成了越来越大的威胁。除了合成新的抗生素，这是一个极其昂贵和耗时的过程外，对抗细菌感染的方法之一是使用金纳米粒子（Au NPs）作为靶向输送治疗药物的载体。由于这种策略需要研究 Au NPs（有和没有药物）对细菌和人类细胞的影响，我们研究了无涂层 Au NPs 的存在如何影响模拟原核（PRO）和真核（EU）细胞的脂质膜的物理化学性质。使用 1,2-二棕榈酰基-sn-甘油-3-磷酸胆碱（DPPC）和 1,2-二棕榈酰基-sn-甘油-3-磷酸甘油（DPPG）/1,2-二棕榈酰基-sn-甘油-3-磷酸丝氨酸（DPPS）制备的多层囊泡（MLVs）和混合结构（HSs）作为 PRO/EU 系统，在没有（MLVs）/存在（HSs）的情况下，不同分布的 Au NPs（尺寸约为 20nm）的存在稳定了 PRO 系统的凝胶相，与 EU 系统相比（PRO/EU 的 DSC 数据为 T(MLVs)≈41.8°C/42.0°C，T¯(HSs)≈43.1°C/42.4°C，而 UV-Vis 响应 T(MLVs)≈41.5°C/42.0°C，T¯(HSs)≈42.9°C/41.1°C）。振动光谱数据揭示了 Au NPs 对脂质双层非极性部分的重大影响，强调了烃链的扭曲和 gauche 构象的增加。通过将后者解释为 Au NPs 诱导的缺陷，当 Au NPs 仅存在于脂质膜之外时，这些缺陷会产生最大的影响，这些发现表明，与类似的 PRO 系统相比，Au NPs 降低了基于 EU 的脂质双层的紧凑性。由于未涂层的 Au NPs 在用作抗菌剂时表现出不良影响，因此本工作的结果有助于认识到 AuNP 功能化是一种调节和逆转这种效应的策略。
