Single particle charge detection mass spectrometry enables molecular characterization of lipid nanoparticles and mRNA packaging.

ABSTRACT: Lipid nanoparticles (LNPs) are effective delivery systems for RNA therapeutics, yet their intrinsic heterogeneity in size and composition make them challenging to characterize. Charge detection mass spectrometry (CDMS) was used to rapidly weigh thousands of individual LNPs. Diameter distributions of empty LNPs from CDMS and cryo-TEM measurements are in excellent agreement demonstrating that these particles are sufficiently stable in the high vacuum environment of the mass spectrometer for accurate mass analysis. A similarly prepared mRNA-packaged LNP sample has a peak mass at ∼70 MDa, 31 MDa higher than that of the empty LNP sample. Four freeze-thaw (FT) cycles of the mRNA-LNPs results in a peak mass at ∼26.5 MDa, indicating significantly degraded LNPs. The degraded LNPs are about 28 % of

SUBMITTER: Miller ZM 

PROVIDER: S-EPMC12807447 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature