宾夕法尼亚大学Michael J. Mitchell研究小组揭示了通过生物物理分析阐明脂质纳米颗粒的性质和结构。这一研究成果发表在2025年10月23日出版的国际学术期刊《自然—生物技术》上。

该研究团队通过应用新兴的基于溶液的生物物理方法，从结构上表征了多分散LNP配方，该方法具有更高的分辨率，并提供了超越尺寸和多分散性的生物物理数据。这些技术包括沉降速度分析超离心、多角度光散射后的场流分馏和同步加速器小角度X射线散射的尺寸排除色谱。课题组人员发现LNPs在大小、RNA负载和形状上具有内在的多分散性，这取决于配方技术和脂质组成。最后，该研究团队通过检测mRNA翻译与理化特性之间的关系来预测LNP在体外和体内的转染。基于解决方案的生物物理方法对于确定LNP结构-功能关系至关重要，有助于LNP新设计规则的创建。

据悉，设计具有特异性靶向、效力和最小副作用的脂质纳米颗粒（LNP）递送系统对其临床主题至关重要。然而，传统的表征方法，如动态光散射，无法准确量化LNPs的物理化学性质以及这些性质如何受到脂质组成和混合方法的影响。

附：英文原文

Title: Elucidating lipid nanoparticle properties and structure through biophysical analyses

Author: Padilla, Marshall S., Shepherd, Sarah J., Hanna, Andrew R., Kurnik, Martin, Zhang, Xujun, Chen, Michelle, Byrnes, James, Joseph, Ryann A., Yamagata, Hannah M., Ricciardi, Adele S., Mrksich, Kaitlin, Issadore, David, Gupta, Kushol, Mitchell, Michael J.

Issue&Volume: 2025-10-23

Abstract: Designing lipid nanoparticle (LNP) delivery systems with specific targeting, potency and minimal side effects is crucial for their clinical use. However, traditional characterization methods, such as dynamic light scattering, cannot accurately quantify physicochemical properties of LNPs and how these are influenced by the lipid composition and mixing method. Here, we structurally characterize polydisperse LNP formulations by applying emerging solution-based biophysical methods that have higher resolution and provide biophysical data beyond size and polydispersity. These techniques include sedimentation velocity analytical ultracentrifugation, field-flow fractionation followed by multiangle light scattering and size-exclusion chromatography in line with synchrotron small-angle X-ray scattering. We show that LNPs have intrinsic polydispersity in size, RNA loading and shape, which depend on both the formulation technique and the lipid composition. Lastly, we predict LNP transfection in vitro and in vivo by examining the relationship between mRNA translation and physicochemical characteristics. Solution-based biophysical methods will be essential for determining LNP structure–function relationships, facilitating the creation of new design rules for LNPs.

DOI: 10.1038/s41587-025-02855-x

Source: https://www.nature.com/articles/s41587-025-02855-x