Glutathione-Responsive Fluorinated Nanogels Enabling Dual-Modal Imaging and Photodynamic Therapy.

19F magnetic resonance imaging (19F MRI) is an emerging non-invasive imaging modality with a high signal-to-noise ratio (SNR) and negligible background interference from biological tissues. However, the hydrophobic nature of fluorine atoms limits both 19F signal intensity and in vivo applicability. Therefore, developing fluorinated MRI contrast agents that combine high fluorine content with good hydrophilicity is essential for advancing in vivo 19F MRI. In this study, a fluorine-containing nanogel (FNG) is synthesized via emulsion polymerization and de-protection using trifluoroethyl methacrylate (TFMA) and tert-butyl acrylate (t-BA). The FNG is then loaded with the near-infrared photosensitizer IR780 to obtain a multifunctional imaging probe (IFNG) capable of dual-modal 19F MR and fluorescence (FL) imaging-guided photodynamic therapy (PDT). The resulting IFNG exhibited a T2 relaxation time of 46.32 ms, confirming its excellent MRI performance in vitro. In the tumor microenvironment, IFNG undergoes glutathione (GSH)-responsive decrosslinking, which exposes the encapsulated IR780. This process enhances fluorescence signal and promotes reactive oxygen species (ROS) generation under near-infrared light, thereby triggering effective PDT. Overall, these findings demonstrate IFNG as a promising nanoplatform that integrates dual-modal 19F MR/FL imaging with GSH-activated photodynamic therapy, offering great potential for precise tumor localization and image-guided cancer treatment.