Water-Soluble Chemically Precise Fluorinated Molecular Clusters for Interference-Free Multiplex 19 F MRI in Living Mice.

Fluorine-19 magnetic resonance imaging ( ¹⁹ F MRI) is gaining widespread interest from the fields of biomolecule detection, cell tracking, and diagnosis, benefiting from its negligible background, deep tissue penetration, and multispectral capacity. However, a wide range of ¹⁹ F MRI probes are in great demand for the development of multispectral ¹⁹ F MRI due to the limited number of high-performance ¹⁹ F MRI probes. Herein, we report a type of water-soluble molecular ¹⁹ F MRI nanoprobe by conjugating fluorine-containing moieties with a polyhedral oligomeric silsesquioxane (POSS) cluster for multispectral color-coded ¹⁹ F MRI. These chemically precise fluorinated molecular clusters are of excellent aqueous solubility with relatively high ¹⁹ F contents and of single ¹⁹ F resonance frequency with suitable longitudinal and transverse relaxation times for high-performance ¹⁹ F MRI. We construct three POSS-based molecular nanoprobes with distinct ¹⁹ F chemical shifts at -71.91, -123.23, and -60.18 ppm and achieve interference-free multispectral color-coded ¹⁹ F MRI of labeled cells in vitro and in vivo . Moreover, in vivo ¹⁹ F MRI reveals that these molecular nanoprobes could selectively accumulate in tumors and undergo rapid renal clearance afterward, illustrating their favorable in vivo behavior for biomedical applications. This study provides an efficient strategy to expand the ¹⁹ F probe libraries for multispectral ¹⁹ F MRI in biomedical research.