Kupffer Cell Capture-Evading Modifiable Sub-20 nm Lipid Nanodisc-Based ¹⁹F Magnetic Resonance Imaging Probes

¹⁹F magnetic resonance imaging (MRI) is an innovative imaging method that enables sensitive visualization of ¹⁹F-containing probes and has been applied to biomedical imaging. A key strategy in probe design is incorporation of a large number of highly mobile ¹⁹F nuclei that can enhance the MRI signal intensity. However, conventional emulsion-based probes are difficult to reduce to below 80 nm in diameter, making them prone to uptake by Kupffer cells and resulting in poor delivery efficiency to target tissues. Moreover, smaller probes based on nanocrystals or polymers suffer from low ¹⁹F mobility, leading to weak signal intensity. In this study, we utilized lipid nanodiscs to confine highly mobile ¹⁹F-labeled lipids, developing sub-20 nm ¹⁹F MRI probes with diameters of approximately 10 nm. The resulting probes exhibited a unique behavior in vivo, distinct from that of conventional probes: they avoided Kupffer cell uptake and were excreted via kidneys. MR signals remained detectable after surface modification. PEGylated nanodiscs exhibited a slower accumulation in the bladder compared with unmodified counterparts, likely due to their prolonged circulation time induced by PEG modification. With the potential to reach tissues previously inaccessible and be modified with various functional moieties, our nanodisc-based platform offers broad opportunities for biomedical applications, including visualization of diverse organs and monitoring of biochemical reactions in vivo.