In recent years, nanoparticles have evolved to a clinical modality to deliver diverse nucleic acids. Rising interest in nanomedicines comes from proven safety and efficacy profiles established by continuous efforts to optimize physicochemical properties and endosomal escape. However, despite their transformative impact on the pharmaceutical industry, the clinical use of non-viral nucleic acid delivery is limited to hepatic diseases and vaccines due to liver accumulation. Overcoming liver tropism of nanoparticles is vital to meet clinical needs in other organs. Understanding the anatomical structure and physiological features of various organs would help to identify potential strategies for fine-tuning nanoparticle characteristics. In this Review, we discuss the source of liver tropism of non-viral vectors, present a brief overview of biological structure, processes and barriers in select organs, highlight approaches available to reach non-liver targets, and discuss techniques to accelerate the discovery of non-hepatic therapies.

近年来，纳米颗粒已发展成为一种递送多种核酸的临床方式。人们对纳米药物日益浓厚的兴趣来自于通过不断努力优化理化性质和内体逃逸而建立的经过验证的安全性和功效。然而，尽管非病毒核酸递送对制药行业产生了变革性影响，但由于肝脏积聚，其临床应用仅限于肝病和疫苗。克服纳米颗粒的肝向性对于满足其他器官的临床需求至关重要。了解各种器官的解剖结构和生理特征将有助于确定微调纳米颗粒特性的潜在策略。在这篇综述中，我们讨论了非病毒载体的肝脏趋向性来源，简要概述了选定器官的生物结构、过程和障碍，重点介绍了可用于达到非肝脏目标的方法，并讨论了加速发现非病毒载体的技术。非肝脏治疗。