Intracellular Self-Assembly and Disassembly of ¹⁹F Nanoparticles Confer Respective “Off” and “On” ¹⁹F NMR/MRI Signals for Legumain Activity Detection in Zebrafish

(19)F MRI has higher selectivity but lower sensitivity than (1)H MRI for in vivo diagnosis. Therefore, to avoid using a high injection dose of the (19)F probe while, in the meantime, maintaining the high sensitivity of (19)F MRI has remained challenging. Local self-assembly and disassembly of (19)F nanoparticles could be one of the "smart" strategies to achieve this goal. Herein, we report a dual-functional probe 1 for glutathione (GSH)-controlled self-assembly and subsequent legumain (Lgmn)-controlled disassembly of its nanoparticles (i.e., 1-NPs). Self-assembly and disassembly of 1-NPs confer (19)F magnetic resonance (MR) signals "off" and "on", respectively. Employing this strategy, we successfully applied 1 for consecutive detections of GSH and Lgmn in vitro and in cells, imaging Lgmn activity in HEK 293T tumors in zebrafish at a low dosage under 14.1 T.