Fluorinated Ionic Liquid Based Multicolor ¹⁹ F MRI Nanoprobes for In Vivo Sensing of Multiple Biological Targets

Multicolor imaging, which maps the distribution of different targets, is important for in vivo molecular imaging and clinical diagnosis. Fluorine 19 magnetic resonance imaging (¹⁹ F MRI) is a promising technique because of unique insights without endogenous background or tissue penetration limit. Thus multicolor ¹⁹ F MRI probes, which can sense a wide variety of molecular species, are expected to help elucidate the biomolecular networks in complex biological systems. Here, a versatile model of activatable probes based on fluorinated ionic liquids (ILs) for multicolor ¹⁹ F MRI is reported. Three types of ILs at different chemical shifts are loaded in nanocarriers and sealed by three stimuli-sensitive copolymers, leading to "off" ¹⁹ F signals. The coating polymers specifically respond to their environmental stimuli, then degrade to release the loaded ILs, causing ¹⁹ F signals recovery. The nanoprobes are utilized for non-invasive detection of tumor hallmarks, which are distinguished by their individual colors in one living mouse, without interference between each other. This multicolor imaging strategy, which adopts modular construction of various ILs and stimuli-responsive polymers, will allow more comprehensive sensing of multiple biological targets, thus, opening a new realm in mechanistic understanding of complex pathophysiologic processes in vivo.