Elastic Polymer Coated Nanoparticles with Fast Clearance for 19F MR Imaging

19F magnetic resonance imaging (MRI) is a powerful molecular imaging technique that enables high‐resolution imaging of deep tissues without background signal interference. However, the use of nanoparticles (NPs) as 19F MRI probes has been limited by the immediate trapping and accumulation of stiff NPs, typically of around 100 nm in size, in the mononuclear phagocyte system, particularly in the liver. To address this issue, elastic nanomaterials have emerged as promising candidates for improving delivery efficacy in vivo. Nevertheless, the impact of elasticity on NP elimination has remained unclear due to the lack of suitable probes for real‐time and long‐term monitoring. In this study, we present the development of perfluorocarbon‐encapsulated polymer NPs as a novel 19F MRI contrast agent, with the aim of suppressing long‐term accumulation. The polymer NPs have high elasticity and exhibit robust sensitivity in 19F MRI imaging. Importantly, our 19F MRI data demonstrate a gradual decline in the signal intensity of the polymer NPs after administration, which contrasts starkly with the behavior observed for stiff silica NPs. This innovative polymer‐coated NP system represents a groundbreaking nanomaterial that successfully overcomes the challenges associated with long‐term accumulation, while enabling tracking of biodistribution over extended periods.