The liver sinusoidal endothelial cells (LSECs) that make up the lining of the liver sinusoids play a vital, but frequently ignored, role in liver physiology, toxicology, and aging. For instance, the LSECs are responsible for a remarkably efficient scavenging of a great number of macromolecules and nanoparticles from the circulation (1). In addition, these cells are equipped with numerous open pores (30–250 nm), or fenestrae, allowing passive passage of macromolecules between the blood (ie, the sinusoidal lumen) and the hepatocytes. In this way, LSECs act like an efficient filter, contributing importantly to homeostasis. LSECs also pose a major challenge to the delivery of large molecule drugs and nano formulations, in that they efficiently scavenge these compounds, preventing them from reaching the tissues where their intended therapeutic effect is to take place. Moreover, certain drugs, of both small and large molecule size, have been shown to cause liver toxicity by having an initial adverse effect on LSECs (2).

中文翻译：

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旧药重振旧肝细胞。

构成肝窦内膜的肝窦内皮细胞 (LSEC) 在肝脏生理学、毒理学和衰老中发挥着重要但经常被忽视的作用。例如，LSEC 负责从循环中非常有效地清除大量大分子和纳米颗粒 (1)。此外，这些细胞配备有许多开孔（30-250 nm）或窗孔，允许大分子在血液（即，肝窦腔）和肝细胞之间被动通过。通过这种方式，LSEC 就像一个有效的过滤器，对体内平衡有重要贡献。LSECs 还对大分子药物和纳米制剂的递送提出了重大挑战，因为它们有效地清除了这些化合物，阻止它们到达将产生预期治疗效果的组织。此外，某些小分子和大分子的药物已被证明会通过对 LSEC 产生初始不利影响而引起肝毒性 (2)。