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

For cancer diagnosis, H-1 magnetic resonance imaging (MRI) is advantageous in sensitivity but lacks selectivity. Endogenous F-19 MRI signal in humans is barely detectable and thus F-19 MRI has very high selectivity. A combination of H-1 and F-19 MRI is ideal for precise tumor imaging but a protease-controlled strategy of simultaneous T-2 H-1 MRI enhancement and F-19 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 T-2 H-1 MRI signal and switching the F-19 NMR/MRI signal On. Using this strategy, IONP@1 is successfully applied to detect the activity of the furin enzyme with Turn-On F-19 NMR/MRI and T-2 H-1 MRI signals are enhanced. Moreover, IONP@1 is also applied for precise dual-mode (H-1 and F-19) 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 H-1 MR and F-19 MR imaging of tumor in mouse or in bigger rodents in near future.