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

Abstract

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.

Plasmonic gold nanoagents for cancer imaging and therapy

“…MRI contrast agents are paramagnetic or superparamagnetic substances, which can make the imaging of the lesion site clearer and improve the sen-sitivity and detection limit of diagnosis. Superparamagnetic iron oxide NP is a common, widely reported MRI contrast agent; [62][63][64] however, these can cause severe protein and DNA damage and inflammation of normal tissue because of the generated reactive oxygen species (ROS). [65][66] Therefore, there is an urgent need to develop a contrast agent with low or no toxicity to meet clinical requirements.…”

Biological functions of supramolecular assemblies of small molecules in the cellular environment

“…10F ). 104 In addition to identifying and inhibiting cancer cells, SASMs are also able to image 106 and inhibit tumors. 105 …”

<p>Perfluorocarbons-Based ¹⁹F Magnetic Resonance Imaging in Biomedicine</p>

“…These 19 F MRI probes are suitable for noninvasive visualization of enzymatic activity, redox-potential difference, and pH. 104,156,157 PFC NPs have been used to monitor specific biological events in living animals with an off/on 19 F MRI switch for detecting enzymatic activity based on the paramagnetic relaxation enhancement effect (PRE) for spin-spin relaxation (T 2 ) of 19 F MRI signal without endogenous background signals. 158 Because of the large electron spin quantum number, Gd 3+ and Mn 2+ have a very strong PRE effect on the MRI signal of 19 F. The shielded 19 F MRI signal of PFC by the adjacent Gd 3+ was triggered to turn on because of the cleavage of enzyme (Figure 4).…”