ROS-Responsive Fluorinated Oxalate Nanomedicine for Dual Chemiluminescence/¹⁹F MRI Imaging and Targeted Drug Release

In this study, we developed a novel theranostic nanomedicine formulation that integrates multimodal imaging with controlled drug release in reactive oxygen species (ROS)-rich microenvironments. A fluorinated oxalate compound (FOC) was synthesized through a one-step condensation reaction between 1,1,1,3,3,3-hexafluoro-2-propanol and oxalyl chloride, characterized by ¹H, ¹³C, and ¹⁹F NMR spectroscopy. The FOC and luminophore-incorporated nanomedicine formulations reacted rapidly with hydrogen peroxide via the peroxyoxalate chemiluminescence (POCL) mechanism, producing strong chemiluminescence and inducing a notable 19-fold increase in ratiometric ¹⁹F NMR signal upon conversion to fluorinated alcohol (FAH), demonstrating promising potential for high-contrast ¹⁹F MRI in deep tissue. Following ROS stimulation, the chemical conversion from hydrophobic FOC to hydrophilic FAH led to the degradation of the nanomedicines, facilitating payload release. In vitro experiments with A-431 cancer cells under hypoxic conditions confirmed ROS-responsive drug release, evidenced by enhanced fluorescence from model luminophores. Additionally, doxorubicin-loaded FOC nanomedicines reduced cell viability to 32% under hypoxia while remaining non-toxic in normoxic conditions. These results indicate that FOC-based nanomedicine formulations provide a promising platform for combined chemiluminescence and ¹⁹F MRI with targeted therapeutic efficacy in ROS-rich inflammatory and cancerous tissues.