pH-Responsive Glycopolymers as Fluorine-19 Magnetic Resonance Imaging Agents Crossing the Blood–Brain Barrier

Fluorine-19 magnetic resonance imaging ( 19 F MRI) facilitates the imaging of deep tissues because of its excellent penetration capabilities and absence of background artifacts, which are very important in biology, medical diagnostics, and neuroscience. The functionality of 19 F MRI is intrinsically linked to the structural composition of its contrast agents (CAs). Modifications with various structural or functional compounds can enhance the contrast, water solubility, biocompatibility, and targeting efficacy of 19 F CAs. Notably, glucose-modified 19 F CAs can cross the blood–brain barrier (BBB). Consequently, we synthesized pH-responsive linear and hyperbranched fluorinated polymers, which crossed the BBB in small-animal imaging experiments and generated weak 19 F signals (OFF) under physiological conditions. However, because of the protonation of their tertiary amine groups, these glycopolymers exhibited the higher mobility of fluorine and generated obvious 19 F signals (ON) under acidic conditions. Furthermore, their biocompatibility was excellent, as confirmed using cytotoxicity and hemolysis tests and hematoxylin and eosin staining. This research establishes a robust foundation for the application of 19 F MRI technology in diagnosing brain diseases.