Diwan Rimpy, Gaytan Samantha Lynn, Bhatt Himanshu Narendrakumar, Pena-Zacarias Jacqueline, Nurunnabi Md
Department of Pharmaceutical Sciences, School of Pharmacy, The University of Texas El Paso, El Paso, TX, 79902, USA.
Department of Biomedical Engineering, College of Engineering, The University of Texas El Paso, El Paso, TX, 79968, USA.
Drug Deliv Transl Res. 2024 Oct;14(10):2743-2770. doi: 10.1007/s13346-024-01551-8. Epub 2024 Mar 6.
Liver fibrosis (LF) occurs when the liver tissue responds to injury or inflammation by producing excessive amounts of scar tissue, known as the extracellular matrix. This buildup stiffens the liver tissue, hinders blood flow, and ultimately impairs liver function. Various factors can trigger this process, including bloodborne pathogens, genetic predisposition, alcohol abuse, non-steroidal anti-inflammatory drugs, non-alcoholic steatohepatitis, and non-alcoholic fatty liver disease. While some existing small-molecule therapies offer limited benefits, there is a pressing need for more effective treatments that can truly cure LF. RNA therapeutics have emerged as a promising approach, as they can potentially downregulate cytokine levels in cells responsible for liver fibrosis. Researchers are actively exploring various RNA-based therapeutics, such as mRNA, siRNA, miRNA, lncRNA, and oligonucleotides, to assess their efficacy in animal models. Furthermore, targeted drug delivery systems hold immense potential in this field. By utilizing lipid nanoparticles, exosomes, nanocomplexes, micelles, and polymeric nanoparticles, researchers aim to deliver therapeutic agents directly to specific biomarkers or cytokines within the fibrotic liver, increasing their effectiveness and reducing side effects. In conclusion, this review highlights the complex nature of liver fibrosis, its underlying causes, and the promising potential of RNA-based therapeutics and targeted delivery systems. Continued research in these areas could lead to the development of more effective and personalized treatment options for LF patients.
肝纤维化（LF）是指肝脏组织在受到损伤或炎症刺激时，产生过量的瘢痕组织，即细胞外基质。这种堆积会使肝脏组织变硬，阻碍血液流动，并最终损害肝功能。多种因素可引发这一过程，包括血源性病原体、遗传易感性、酒精滥用、非甾体抗炎药、非酒精性脂肪性肝炎和非酒精性脂肪肝。虽然现有的一些小分子疗法效果有限，但迫切需要能真正治愈肝纤维化的更有效治疗方法。RNA疗法已成为一种有前景的方法，因为它们有可能下调导致肝纤维化的细胞中的细胞因子水平。研究人员正在积极探索各种基于RNA的疗法，如信使核糖核酸（mRNA）、小干扰核糖核酸（siRNA）、微小核糖核酸（miRNA）、长链非编码核糖核酸（lncRNA）和寡核苷酸，以评估它们在动物模型中的疗效。此外，靶向给药系统在该领域具有巨大潜力。通过利用脂质纳米颗粒、外泌体、纳米复合物、胶束和聚合物纳米颗粒，研究人员旨在将治疗剂直接递送至纤维化肝脏内的特定生物标志物或细胞因子，提高其有效性并减少副作用。总之，本综述强调了肝纤维化的复杂性、其潜在病因以及基于RNA的疗法和靶向给药系统的广阔前景。在这些领域持续开展研究可能会为肝纤维化患者开发出更有效、更个性化的治疗方案。
