For drug delivery systems the mechanical properties of the 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 mechanical parperties 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 use AFM to image and probe the mechanical properties of LNP which are either loaded with two different biopolymers either pDNA or mRNA. Imaging the LNP before and after the indentation as well as recording the retraction curve enables us to obtain more insight on 1 how the AFM tip penetrates into the particle and to determine whether the deformation of the LNP is reversible. For pDNA, the indentation by the tip leads to the 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 paves the way toward the establishment of the link between the LNP formulation and the delivery efficiency.