Furin‐Controlled Fe 3 O 4 Nanoparticle Aggregation and 19 F Signal “Turn‐On” for Precise MR Imaging of Tumors

For cancer diagnosis, 1 H magnetic resonance imaging (MRI) is advantageous in sensitivity but lacks selectivity. Endogenous 19 F MRI signal in humans is barely detectable and thus 19 F MRI has very high selectivity. A combination of 1 H and 19 F MRI is ideal for precise tumor imaging but a protease‐controlled strategy of simultaneous T 2 1 H MRI enhancement and 19 F MRI “Turn‐On” has not been reported. Here, used is a click condensation reaction to rationally project a dual‐functional fluorine probe 4‐(trifluoromethyl)benzoic acid (TFMB)‐Arg‐Val‐Arg‐Arg‐Cys(StBu)‐Lys‐CBT ( 1 ), which is further utilized to functionalize Fe 3 O 4 nanoparticle ( IONP ) to achieve IONP@1 . As such, the IONP aggregation can be activated by furin addition, thereby enhancing the T 2 1 H MRI signal and switching the 19 F NMR/MRI signal “On”. Using this strategy, IONP@1 is successfully applied to detect the activity of the furin enzyme with “Turn‐On” 19 F NMR/MRI and T 2 1 H MRI signals are enhanced. Moreover, IONP@1 is also applied for precise dual‐mode ( 1 H and 19 F) MR imaging of tumors in zebrafish under 14.1 T. The current approach, therefore, provides a feasible and robust means to reconcile the dilemma between selectivity and sensitivity of conventional MRI probes. More importantly, it is envisioned that, by substituting the TFMB moiety in 1 with a perfluorinated compound, this “smart” method could be of potential use for precise 1 H MR and 19 F MR imaging of tumor in mouse or in bigger rodents in near future.