Switchable Photoacoustic Imaging of Glutathione Using MnO₂ Nanotubes for Cancer Diagnosis

Glutathione is overexpressed in tumor cells and regulates cancer growth, metastasis, and drug resistance. Therefore, detecting glutathione levels may greatly facilitate cancer diagnosis and treatment response monitoring. Photoacoustic (PA) imaging is a noninvasive modality for high-sensitivity, high-resolution, deep-tissue optical imaging. Switchable PA probes that offer signal on/off responses to tumor targets would further improve the detection sensitivity and signal-to-noise ratio of PA imaging. Here, we explore the use of MnO 2 nanotubes as a switchable and biodegradable PA probe for dynamic imaging of glutathione in cancer. Glutathione reduces black MnO 2 nanotubes into colorless Mn 2+ ions, leading to decreased and signal off PA amplitude. In phantoms, we observed a linear response of reduced PA signals of MnO 2 nanotubes to increased glutathione concentrations. Using melanoma as the disease model, we demonstrated that MnO 2 nanotube-based PA imaging of glutathione successfully distinguished B16F10 melanoma cells from BEAS-2B normal cells and discriminated B16F10 tumors from healthy skin tissues. Our results showed that MnO 2 nanotubes are a potent switchable and biodegradable PA probe for glutathione imaging in cancer diagnosis.