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

Abstract

Compared to (1)H MRI, (19)F MRI provides higher selectivity but lower sensitivity. Therefore, the need to inject high doses of the (19)F probe to improve its sensitivity for in vivo diagnosis remains a challenge. A "smart" strategy is needed that could locally concentrate a low-dose (19)F probe while avoiding the fast transverse relaxation of the probes. Locally self-assembling and disassembling (19)F 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" (19)F 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.

Rapid and recoverable in vivo magnetic resonance imaging of the adult zebrafish at 7T

“…In general, such reports have used pre-existing MRI coils that are not tailored to the species, including the use of expensive cryogenic coils to boost signal reception. Many of these previous studies have been performed using ex vivo or fixed fish [26], [27], [28] as opposed to our system that uses live subjects with full recovery.…”

A Programmed Nanoparticle with Self-Adapting for Accurate Cancer Cell Eradication and Therapeutic Self-Reporting

“…In addition, the therapeutic self-monitoring could be achieved simultaneously to further enhance the anticancer efficacy 23-25. Given the critical roles of caspase-3 in cell-death process, various caspase-3 activatable imaging reagents 26, including 19 F magnetic resonance imaging probe 27, positron emission tomography tracer 28, quantum dot sensor 29 and fluorescence probe 30, have been developed for reporting the apoptotic information. These approaches offer good opportunity to easily investigate treatment-to-effect correlations.…”

Design and Synthesis of Fluorinated Amphiphile as 19F MRI/Fluorescence Dual-Imaging Agent by Tuning the Self-Assembly

“…11, 14 In this case, we demonstrated that 19 F NMR signal can be turned on by tuning the particle size and shape by either breaking the coplanarity or improving the hydrophilicity. Therefore, it is crucial to take selfassembly into consideration during the design of novel amphiphilic 19 F MRI agents.…”