Department of Chemical Engineering, Osaka Metropolitan University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan.
Phys Chem Chem Phys. 2024 Aug 7;26(31):21229-21239. doi: 10.1039/d4cp00330f.
Nanoparticles (NPs) have attracted significant attention as carriers for the delivery of drugs, genes, and macromolecules for biomedical and therapeutic applications. These technologies require NPs to be delivered to the interior of the cell. However, this translocation is unlikely because of the presence of a cell membrane composed of phospholipids, cholesterol, proteins, and glycans. The cell membrane composition can influence its rigidity; thus, membrane composition is a crucial factor in determining the translocation of NPs across the cell membrane. Here, we focus on cholesterol, which is an essential component of biological cell membranes, and investigate NP translocation across membranes containing cholesterol under an applied electric field using a coarse-grained molecular dynamics simulation. We found that NPs could translocate directly across cholesterol-containing membranes without irreversible membrane disruption. This unique translocation was induced by two key phenomena. Before NP translocation, a phospholipid-rich/cholesterol-poor domain was formed at the NP-membrane contact interface. Second, a smaller transmembrane pore was formed in the cholesterol-containing membrane during membrane crossing of the NP. Our findings imply that the delivery of NPs to the cell interior across the cholesterol-containing membrane can be achieved by appropriately controlling the strength of the applied electric field, depending on the cholesterol content in the membrane.
纳米颗粒 (NPs) 作为药物、基因和生物大分子的载体，在生物医学和治疗应用中引起了广泛关注。这些技术需要将 NPs 递送到细胞内部。然而，由于细胞膜由磷脂、胆固醇、蛋白质和聚糖组成，这种转位不太可能发生。细胞膜的组成会影响其刚性；因此，膜组成是决定 NPs 跨细胞膜转位的关键因素。在这里，我们专注于胆固醇，它是生物细胞膜的重要组成部分，并使用粗粒分子动力学模拟研究了在施加电场下含有胆固醇的 NP 跨膜转运。我们发现，NP 可以直接穿过含有胆固醇的膜而不发生不可逆的膜破坏。这种独特的转位是由两个关键现象引起的。在 NP 转位之前，在 NP-膜接触界面处形成了富含磷脂/胆固醇贫乏的区域。其次，在 NP 穿过膜时，在含有胆固醇的膜中形成了一个较小的跨膜孔。我们的研究结果表明，通过适当控制施加电场的强度，可以将 NP 递送到含有胆固醇的膜内的细胞内部，具体取决于膜中的胆固醇含量。
