Lipid Bilayer–Coated Core–Shell Silica Nanoparticles with Enhanced Clearance and Biocompatibility for High Sensitivity ¹⁹ F Magnetic Resonance Imaging

The development of noninvasive, quantifiable molecular imaging probes using magnetic resonance imaging (MRI) is critical for advancing in vivo diagnostics. Previous work has demonstrated the development of perfluorocarbon (PFC)‐encapsulated silica nanoparticles named as FLAME (fluorine accumulated silica nanoparticles for MRI enhancement) for sensitive in vivo imaging using 19 F MRI. While FLAME shows excellent MR properties and application potential, its biocompatibility is yet to be enhanced. Herein, a lipid bilayer‐coated 19 F MRI nanoparticle (FLAME‐LB) is developed, which easily changes the surface components of nanoparticles by coating PFC‐loaded silica nanoparticles with a phospholipid membrane containing PEGylated lipids. Structural characterization confirmed the successful bilayer formation, and 19 F nuclear magnetic resonance (NMR)/MRI analyses demonstrated strong, concentration‐dependent fluorine signals. In vivo studies in mice reveal that FLAME‐LB accumulates in the liver shortly after intravenous injection, but exhibits significantly faster clearance than uncoated FLAME nanoparticles. This difference is attributed to the lipid bilayer and PEGylation, which promotes hepatobiliary elimination. These findings highlight the potential of the surface‐engineered FLAME‐LB as a biocompatible and tunable platform for 19 F MRI applications in biomedical imaging.