Udepurkar Aniket, Devos Cedric, Sagmeister Peter, Destro Francesco, Inguva Pavan, Ahmadi Soroush, Boulais Etienne, Quan Yufeng, Braatz Richard D, Myerson Allan S
Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
ACS Nano. 2025 Jun 17;19(23):21206-21242. doi: 10.1021/acsnano.4c18274. Epub 2025 Jun 3.
Lipid nanoparticles (LNPs) are a clinically proven platform for protecting and delivering nucleic acid-based therapeutics. These multicomponent particles self-assemble into a core-shell structure with the nucleic acid cargo encapsulated in its core. Despite considerable research efforts to establish structure-efficacy relationships, their morphological and structural characteristics─particularly their internal composition and distribution─remain elusive. This uncertainty arises from several factors, including challenges in characterization, the dynamic nature of LNPs, sample heterogeneity, and poorly understood formulation-structure relationships. This review highlights the current state of research on the structure and morphology of LNPs, characterization techniques, and ongoing efforts to elucidate how formulation parameters affect the structural and morphological LNP properties.
脂质纳米颗粒（LNPs）是一种经临床验证的用于保护和递送基于核酸的治疗药物的平台。这些多组分颗粒自组装成核壳结构，核酸有效载荷包裹在其核心中。尽管为建立结构-功效关系付出了大量研究努力，但其形态和结构特征——尤其是其内部组成和分布——仍然难以捉摸。这种不确定性源于几个因素，包括表征方面的挑战、LNPs的动态性质、样品的异质性以及对配方-结构关系的了解不足。本综述重点介绍了LNPs结构和形态的研究现状、表征技术，以及为阐明配方参数如何影响LNP的结构和形态特性而正在进行的努力。
