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

Abstract

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.