Protein corona formed on lipid nanoparticles compromises delivery efficiency of mRNA cargo.

ABSTRACT: Lipid nanoparticles (LNPs) are the most clinically advanced nonviral RNA-delivery vehicles, though challenges remain in fully understanding how LNPs interact with biological systems. In vivo, proteins form an associated corona on LNPs that redefines their physicochemical properties and influences delivery outcomes. Despite its importance, the LNP protein corona is challenging to study owing to the technical difficulty of selectively recovering soft nanoparticles from biological samples. Herein, we develop a quantitative, label-free mass spectrometry-based proteomics approach to characterize the protein corona on LNPs. Critically, this protein corona isolation workflow avoids artifacts introduced by the presence of endogenous nanoparticles in human biofluids. We apply continuous density gra

SUBMITTER: Voke E 

PROVIDER: S-EPMC12485112 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature