Dual Nanoparticle Conjugates for Highly Sensitive and Versatile Sensing Using ¹⁹ F Magnetic Resonance Imaging

Fluorine magnetic resonance imaging (¹⁹ F MRI) has emerged as an attractive alternative to conventional ¹ H MRI due to enhanced specificity deriving from negligible background signal in this modality. We report a dual nanoparticle conjugate (DNC) platform as an aptamer-based sensor for use in ¹⁹ F MRI. DNC consists of core-shell nanoparticles with a liquid perfluorocarbon core and a mesoporous silica shell (¹⁹ F-MSNs), which give a robust ¹⁹ F MR signal, and superparamagnetic iron oxide nanoparticles (SPIONs) as magnetic quenchers. Due to the strong magnetic quenching effects of SPIONs, this platform is uniquely sensitive and functions with a low concentration of SPIONs (4 equivalents) relative to ¹⁹ F-MSNs. The probe functions as a "turn-on" sensor using target-induced dissociation of DNA aptamers. The thrombin binding aptamer was incorporated as a proof-of-concept (DNC_Thr ), and we demonstrate a significant increase in ¹⁹ F MR signal intensity when DNC_Thr is incubated with human α-thrombin. This proof-of-concept probe is highly versatile and can be adapted to sense ATP and kanamycin as well. Importantly, DNC_Thr generates a robust ¹⁹ F MRI "hot-spot" signal in response to thrombin in live mice, establishing this platform as a practical, versatile, and biologically relevant molecular imaging probe.