Laboratoire Sciences et Ingénierie de la Matière Molle, CNRS UMR 7615, PSL University, Sorbonne University, ESPCI Paris, 10 rue Vauquelin, Cedex 05 75231 Paris, France.
Sanofi Pasteur, 1541 av Marcel Mérieux, 69280 Marcy l'Etoile, France.
Nanoscale. 2024 Jun 6;16(22):10706-10714. doi: 10.1039/d3nr06543j.
For drug delivery systems, the mechanical properties of drug carriers are suspected to play a crucial role in the delivery process. However, there is a lack of reliable methods available to measure the mechanical properties of drug carriers, which hampers the establishment of a link between delivery efficiency and the mechanical properties of carriers. Lipid nanoparticles (LNPs) are advanced systems for delivering nucleic acids to target cell populations for vaccination purposes (mRNA) or the development of new drugs. Hence, it is crucial to develop reliable techniques to measure the mechanical properties of LNPs. In this article, we used AFM to image and probe the mechanical properties of LNPs which are loaded with two different biopolymers either pDNA or mRNA. Imaging the LNPs before and after indentation, as well as recording the retraction curve, enables us to obtain more insight into how the AFM tip penetrates into the particle and to determine whether the deformation of the LNPs is reversible. For pDNA, the indentation by the tip leads to irreversible rupture of the LNPs, while the deformation is reversible for the mRNA-loaded LNPs. Moreover, the forces reached for pDNA are higher than for mRNA. These results pave the way toward the establishment of the link between the LNP formulation and the delivery efficiency.
对于药物输送系统，药物载体的机械性能被怀疑在输送过程中起着关键作用。然而，目前缺乏可靠的方法来测量药物载体的机械性能，这阻碍了输送效率与载体机械性能之间建立联系。脂质纳米粒（LNPs）是一种先进的系统，可将核酸递送至目标细胞群，用于疫苗接种（mRNA）或开发新药。因此，开发可靠的技术来测量 LNPs 的机械性能至关重要。在本文中，我们使用 AFM 对负载两种不同生物聚合物（pDNA 或 mRNA）的 LNPs 进行成像和探测其机械性能。在压痕前后对 LNPs 进行成像，并记录回缩曲线，使我们能够更深入地了解 AFM 针尖如何穿透颗粒，并确定 LNPs 的变形是否可逆。对于 pDNA，针尖的压痕导致 LNPs 不可逆破裂，而负载 mRNA 的 LNPs 的变形是可逆的。此外，pDNA 达到的力高于 mRNA。这些结果为建立 LNP 配方与输送效率之间的联系铺平了道路。
