Mitochondrial Unfolded Protein Responsive Imaging and Surgical Navigation in Ovarian Cancer

Unfolded proteins, as critical biomarkers in cancer, hold significant potential for tumor-specific imaging. However, the content of unfolded proteins within distinct subcellular organelles varies markedly and reflects divergent physiological implications. Currently, few fluorescent probes enable precise quantification and imaging of mitochondrial unfolded proteins. Herein, we report a fluorescent probe, MAP, for accurate imaging of mitochondrial unfolded proteins. MAP incorporates a triphenylphosphonium group that specifically targets mitochondria, with cellular uptake efficiency proportional to mitochondrial membrane potential. Within mitochondria, the maleimide moiety of MAP covalently reacts with thiol groups on unfolded proteins, restricting molecular rotation and suppressing intramolecular charge transfer (ICT), thereby triggering a significant fluorescence enhancement. Owing to the hyperpolarized mitochondrial membrane potential and abundant mitochondrial unfolded proteins in SKOV3 cells, MAP with superior biocompatibility achieves tumor-specific imaging with a high signal-to-noise ratio (9.5), enabling precise intraoperative navigation for ovarian cancer resection. This molecular design strategy provides a foundational framework for developing organelle-specific unfolded protein probes and advancing image-guided surgical applications.