肝纤维化病理和基于 RNA 的潜在治疗方法。

IF 5.7 3区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Drug Delivery and Translational Research Pub Date : 2024-10-01 Epub Date: 2024-03-06 DOI:10.1007/s13346-024-01551-8
Rimpy Diwan, Samantha Lynn Gaytan, Himanshu Narendrakumar Bhatt, Jacqueline Pena-Zacarias, Md Nurunnabi
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引用次数: 0

摘要

当肝脏组织对损伤或炎症做出反应,产生过量的瘢痕组织(即细胞外基质)时,就会发生肝纤维化(LF)。这种堆积会使肝组织变得僵硬,阻碍血液流动,最终损害肝功能。引发这一过程的因素有很多,包括血液传播的病原体、遗传倾向、酗酒、非类固醇抗炎药物、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疗效有限,但人们迫切需要更有效的治疗方法来真正治愈 LF。RNA 疗法是一种很有前景的方法,因为它们有可能降低导致肝纤维化的细胞因子水平。研究人员正在积极探索各种基于 RNA 的疗法,如 mRNA、siRNA、miRNA、lncRNA 和寡核苷酸,以评估它们在动物模型中的疗效。此外,靶向给药系统在这一领域也具有巨大潜力。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药物直接输送到纤维化肝脏内的特定生物标志物或细胞因子,从而提高疗效并减少副作用。总之,本综述强调了肝纤维化的复杂性、其根本原因以及基于 RNA 的疗法和靶向递送系统的巨大潜力。在这些领域的持续研究可为肝纤维化患者开发出更有效、更个性化的治疗方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Liver fibrosis pathologies and potentials of RNA based therapeutics modalities.

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.

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来源期刊
Drug Delivery and Translational Research
Drug Delivery and Translational Research MEDICINE, RESEARCH & EXPERIMENTALPHARMACOL-PHARMACOLOGY & PHARMACY
CiteScore
11.70
自引率
1.90%
发文量
160
期刊介绍: The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions. Research focused on the following areas of translational drug delivery research will be considered for publication in the journal. Designing and developing novel drug delivery systems, with a focus on their application to disease conditions; Preclinical and clinical data related to drug delivery systems; Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes Short-term and long-term biocompatibility of drug delivery systems, host response; Biomaterials with growth factors for stem-cell differentiation in regenerative medicine and tissue engineering; Image-guided drug therapy, Nanomedicine; Devices for drug delivery and drug/device combination products. In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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