Furin‐Controlled Fe3O4 Nanoparticle Aggregation and 19F Signal “Turn‐On” for Precise MR Imaging of Tumors

For cancer diagnosis, ¹H magnetic resonance imaging (MRI) is advantageous in sensitivity but lacks selectivity. Endogenous ¹⁹F MRI signal in humans is barely detectable and thus ¹⁹F MRI has very high selectivity. A combination of ¹H and ¹⁹F MRI is ideal for precise tumor imaging but a protease‐controlled strategy of simultaneous T₂ ¹H MRI enhancement and ¹⁹F 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 Fe₃O₄ nanoparticle ( IONP ) to achieve IONP@1 . As such, the IONP aggregation can be activated by furin addition, thereby enhancing the T₂ ¹H MRI signal and switching the ¹⁹F NMR/MRI signal “On”. Using this strategy, IONP@1 is successfully applied to detect the activity of the furin enzyme with “Turn‐On” ¹⁹F NMR/MRI and T₂ ¹H MRI signals are enhanced. Moreover, IONP@1 is also applied for precise dual‐mode (¹H and ¹⁹F) 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 ¹H MR and ¹⁹F MR imaging of tumor in mouse or in bigger rodents in near future.