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

Fluorine-19 magnetic resonance imaging (¹⁹F 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 ¹⁹F MRI probes are in great demand for the development of multispectral ¹⁹F MRI due to the limited number of high-performance ¹⁹F MRI probes. Herein, we report a type of water-soluble molecular ¹⁹F MRI nanoprobe by conjugating fluorine-containing moieties with a polyhedral oligomeric silsesquioxane (POSS) cluster for multispectral color-coded ¹⁹F MRI. These chemically precise fluorinated molecular clusters are of excellent aqueous solubility with relatively high ¹⁹F contents and of single ¹⁹F resonance frequency with suitable longitudinal and transverse relaxation times for high-performance ¹⁹F MRI. We construct three POSS-based molecular nanoprobes with distinct ¹⁹F chemical shifts at -71.91, -123.23, and -60.18 ppm and achieve interference-free multispectral color-coded ¹⁹F MRI of labeled cells in vitro and in vivo. Moreover, in vivo ¹⁹F 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 ¹⁹F probe libraries for multispectral ¹⁹F MRI in biomedical research.