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

Abstract

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.

Silicon-containing nanomedicine and biomaterials: materials chemistry, multi-dimensional design, and biomedical application

“…in a single-site or multi-site manner. 375 They can function as a single-molecular nanoplatform or assemble into nanoparticles of relatively large size for drug delivery, fluorescent imaging, tissue engineering, and therapeutic applications. [376][377][378][379] For instance, an organic-inorganic hybrid POSS-porphyrin photosensitizer was synthesized by conjugating porphyrin-N 3 to (vinyl) 7 -POSS-alkyne via copper-catalyzed click chemistry.…”

Glycan Metabolic Fluorine Labeling for In Vivo Visualization of Tumor Cells and In Situ Assessment of Glycosylation Variations

“…Among other nuclei suitable for MRI, 19 F draws the attention of the research community because of its high MR sensitivity (comparable to that of 1 H), 100 % natural abundance, and negligible biological background [24–31] . Besides, the wide range of 19 F chemical shifts (>350 ppm) and the diversity of biocompatible fluorine‐containing agents permit multi‐spectral color‐coded 19 F MRI that is capable of tracing multiple targets [32–36] . In addition, in vivo quantitative analysis, which is difficult for many imaging techniques, is enabled by the quantitative nature of MR and the low biological background of 19 F [37–38] .…”

Fluorinated hydrogel nanoparticles with regulable fluorine contents andT2relaxation times as19F MRI contrast agents

“…Thus, exploring facile strategies to fabricate highperformance 19 F MRI CAs with acceptable preparation procedures still requires attention and effort. Some research has revealed that to achieve high-resolution in vivo 19 F MRI, a very high concentration of 19 F MRI CAs (above 50 mM) is normally administrated, [47][48][49] which indicates that prolonging the circulation time of the 19 F MRI CAs in vessels in vivo and promoting their accumulation inside the imaging lesion in vivo are pivotal as well. Thus, fabricating high-performance 19 F MRI CAs with a long T 2 relaxation time and long circulation time in vivo and with excellent biocompatibility by a simple, efficient, and economical strategy demands increasing attention from researchers.…”