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

Abstract

AbstractFor 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.