Integrating Fluorinated Polymer and Manganese‐Layered Double Hydroxide Nanoparticles as pH‐activated 19 F MRI Agents for Specific and Sensitive Detection of Breast Cancer

19 F magnetic resonance imaging ( 19 F MRI) agents capable of being activated upon interactions with cancer triggers are attracting increasing attention, although challenges still remain for precise and specific detection of cancer tissues. In this study, a novel hybrid 19 F MRI agent for pH‐sensitive detection of breast cancer tissues is reported, a composite system designed by conjugating a perfluoropolyether onto the surface of manganese‐incorporated layered double hydroxide (Mn‐LDH@PFPE) nanoparticles. The 19 F NMR/MRI signals from aqueous solutions of Mn‐LDH@PFPE nanoparticles are quenched at pH 7.4, but “turned on” following a reduction in pH to below 6.5. This is due to partial dissolution of Mn 2+ from the Mn‐LDH nanoparticles and subsequent reduction in the effect of paramagnetic relaxation. Significantly, in vivo experiments reveal that an intense 19 F MR signal can be detected only in the breast tumor tissue after intravenous injection of Mn‐LDH@PFPE nanoparticles due to such a specific activation. Thus pH‐activated Mn‐LDH@PFPE nanoparticles are a potential “smart” 19 F MRI agent for precise and specific detection of cancer diseases.