Hosseini-Kharat Mahboubeh, Bremmell Kristen E, Prestidge Clive A
Clinical and Health Sciences, Centre for Pharmaceutical Innovation, University of South Australia, Adelaide, SA 5000, Australia.
Mol Ther Methods Clin Dev. 2025 Feb 15;33(1):101436. doi: 10.1016/j.omtm.2025.101436. eCollection 2025 Mar 13.
Lipid nanoparticles (LNPs) are now highly effective transporters of nucleic acids to the liver. This liver-specificity is largely due to their association with certain serum proteins, most notably apolipoprotein E (ApoE), which directs them to liver cells by binding to the low-density lipoprotein (LDL) receptors on hepatocytes. The liver's distinct anatomy, with its various specialized cell types, also influences how LNPs are taken up from the circulation, cleared, and how effective they are in delivering treatments. In this review, we consider factors that facilitate LNP's effective liver targeting and explore the latest advances in liver-targeted LNP technologies. Understanding how LNPs are targeted to the liver can help for effective design and optimization of nanoparticle-based therapies. Comprehension of the cellular interaction and biodistribution of LNPs not only leads to better treatments for liver diseases but also delivers insight for directing nanoparticles to other tissues, potentially broadening their range of therapeutic applications.
脂质纳米颗粒（LNPs）目前是将核酸转运至肝脏的高效载体。这种肝脏特异性很大程度上归因于它们与某些血清蛋白的结合，最显著的是载脂蛋白E（ApoE），它通过与肝细胞上的低密度脂蛋白（LDL）受体结合，将脂质纳米颗粒导向肝细胞。肝脏独特的解剖结构及其各种特殊细胞类型，也影响着脂质纳米颗粒如何从循环中摄取、清除，以及它们在递送治疗药物方面的有效性。在本综述中，我们考虑促进脂质纳米颗粒有效肝脏靶向的因素，并探索肝脏靶向脂质纳米颗粒技术的最新进展。了解脂质纳米颗粒如何靶向肝脏有助于有效设计和优化基于纳米颗粒的疗法。理解脂质纳米颗粒的细胞相互作用和生物分布不仅能带来更好的肝脏疾病治疗方法，还能为将纳米颗粒导向其他组织提供思路，有可能拓宽它们的治疗应用范围。
