Controlled Intracellular Self-Assembly and Disassembly of F-19 Nanoparticles for MR Imaging of Caspase 3/7 in Zebrafish

Compared to H-1 MRI, F-19 MRI provides higher selectivity but lower sensitivity. Therefore, the need to inject high doses of the 19F probe to improve its sensitivity for in vivo diagnosis remains a challenge. A smart strategy is needed that could locally concentrate a low-dose F-19 probe while avoiding the fast transverse relaxation of the probes. Locally self-assembling and disassembling F-19 nanoparticles may be an optimal measure to achieve this goal. Herein, we report a dual-functional probe 1 for glutathione (GSH)-controlled self-assembly and subsequent caspase 3/7 (Casp3/7)-controlled disassembly of formed nanoparticles (i.e., 1-NPs). Consecutive assembly and disassembly of 1-NPs translate to off and on F-19 magnetic resonance (MR) signal states, respectively. Employing this smart strategy, we successfully used 1 for the consecutive detection of GSH and Casp3/7 activity in vitro and in cells and imaging Casp3/7 activity in cells and in zebrafish at low doses with a 14.1 T magnetic field.