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.