Superhydrophilic Fluorinated Polymer Probe for Zero-Background ¹⁹F MRI with Adaptable Targeting Ability

¹⁹F magnetic resonance imaging (¹⁹F MRI), with zero background, high tissue penetration depth, excellent spatial resolution, and nonradioactive features, has attracted considerable attention but faces tough challenges due to the shortage of sensitive and selective targetable probes. Herein, we report a biocompatible and highly sensitive ¹⁹F MRI probe with an adaptable tumor-targeting ability. The fluorine-grafted polymer (PIBMA-F_SON) probes were rich with sulfoxide and carboxy groups, containing a high fluorine content (∼17 wt %). The probes exhibit superhydrophilicity, strong ¹⁹F MRI signals (enhancement of ∼95-fold), long transverse relaxation time (<i>T</i>₂, 422 ms), and excellent ¹⁹F MRI capability. Conjugation using a targeting peptide (Arg-Gly-Asp, RGD) afforded ultrasmall soft polymer probes (PIBMA-F_SON-RGD) with superhydrophilicity and tumor-targeting ability suitable for the ¹⁹F MRI of orthotopic bladder cancer. Amidification of 5% of the carboxylate units with oleylamine resulted in PIBMA_OAm-F_SON nanoprobes (NPs) via self-assembly, displaying different targeting toward subcutaneous tumors. Further grafting with near-infrared (NIR) dyes renders the probe suitable for NIR-fluorescence and ¹⁹F MRI dual-modality imaging. This study provides a suitable approach for designing highly sensitive and zero-background ¹⁹F MRI probes with a tunable tumor-targeting ability.