Jabłonowska Elżbieta, Matyszewska Dorota, Nazaruk Ewa, Godlewska Marlena, Gaweł Damian, Bilewicz Renata
Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
Faculty of Chemistry, Biological and Chemical Research Centre, University of Warsaw, Zwirki i Wigury 101, 02-089 Warsaw, Poland.
Biochim Biophys Acta Gen Subj. 2021 Jan;1865(1):129738. doi: 10.1016/j.bbagen.2020.129738. Epub 2020 Sep 18.
The interactions of liquid-crystalline nanoparticles based on lipid-like surfactants, glyceryl monooleate, monoolein (GMO) and 1,2,3-trihydroxy-3,7,11,15-tetramethylhexadecane, phytantriol (PT) with selected model lipid membranes prepared by Langmuir technique were compared. Monolayers of DPPC, DMPS and their mixture DPPC:DMPS 87:13 mol% were used as simple models of one leaflet of a cell membrane. The incorporation of cubosomes into the lipid layers spread at the air-water interface was followed by surface-pressure measurements and Brewster angle microscopy. The cubosome - membrane interactions lead to the fluidization of the model membranes but this effect depended on the composition of the model membrane and on the type of cubosomes. The interactions of PT cubosomes with lipid layers, especially DMPS-based monolayer were stronger compared with those of GMO-based nanoparticles. The kinetics of incorporation of cubosomal material into the lipid layer was influenced by the extent of hydration of the polar headgroups of the lipid: faster in the case of smaller, less hydrated polar groups of DMPS than for strongly hydrated uncharged choline of DPPC. The membrane disrupting effect of cubosomes increased at longer times of the lipid membrane exposure to the cubosome solution and at larger carrier concentrations. Langmuir monolayer observations correspond well to results of studies of HeLa cells exposed to cubosomes. The larger toxicity of PT cubosomes was confirmed by MTS. Their ability to disrupt lipid membranes was imaged by confocal microscopy. On the other hand, PT cubosomes easily penetrated cellular membranes and released cargo into various cellular compartments more effectively than GMO-based nanocarriers. Therefore, at low concentrations, they may be further investigated as a promising drug delivery tool.
比较了基于类脂表面活性剂、甘油单油酸酯、单油酸甘油酯（GMO）和1,2,3 - 三羟基 - 3,7,11,15 - 四甲基十六烷（植烷三醇，PT）的液晶纳米颗粒与通过朗缪尔技术制备的选定模型脂质膜之间的相互作用。DPPC、DMPS及其混合物DPPC:DMPS 87:13 mol%的单层用作细胞膜单叶的简单模型。通过表面压力测量和布鲁斯特角显微镜观察，追踪立方液晶纳米粒掺入在气 - 水界面铺展的脂质层中的情况。立方液晶纳米粒与膜的相互作用导致模型膜的流化，但这种效应取决于模型膜的组成和立方液晶纳米粒的类型。与基于GMO的纳米颗粒相比，PT立方液晶纳米粒与脂质层的相互作用更强，尤其是与基于DMPS的单层。立方液晶纳米粒物质掺入脂质层的动力学受脂质极性头基团水合程度的影响：对于DMPS较小、水合程度较低的极性基团，其掺入速度比DPPC强水合的不带电胆碱更快。脂质膜暴露于立方液晶纳米粒溶液的时间越长以及载体浓度越大，立方液晶纳米粒的膜破坏作用增强。朗缪尔单层观察结果与暴露于立方液晶纳米粒的HeLa细胞的研究结果非常吻合。MTS证实了PT立方液晶纳米粒具有更大的毒性。其破坏脂质膜的能力通过共聚焦显微镜成像。另一方面，PT立方液晶纳米粒比基于GMO的纳米载体更容易穿透细胞膜并更有效地将货物释放到各种细胞区室中。因此，在低浓度下，它们作为一种有前景的药物递送工具可能值得进一步研究。
