Activatable NIR-II photoacoustic probes for cancer imaging and imaging-guided therapy

Photoacoustic (PA) imaging in the second near-infrared (NIR-II) window offers a compelling approach for deep-tissue tumor imaging. However, most reported NIR-II PA probes are "always on", resulting in persistent background signals that limit their imaging specificity and signal-to-background ratios. To address these limitations, activatable NIR-II PA probes that remain "off" under normal physiological conditions have been developed. Upon entering tumor microenvironment, they undergo tumor biomarker-mediated activation and turn "on". Therefore, this stimulus-responsive strategy significantly reduces background interference and enables highly specific cancer imaging. Additionally, the intrinsic photothermal conversion capability of NIR-II PA probes makes them ideal platform for imaging-guided cancer therapy. This review focuses on the recent development in activatable NIR-II PA probes that respond to tumor-related biomarkers, including pH, reactive oxygen species, nitric oxide, glutathione, and enzymes. Then, we highlight recent advances in NIR-II PA imaging-guided cancer therapy based on activatable probes. Finally, current challenges and future perspectives for developing intelligent NIR-II PA theranostic systems are discussed. This review aims to provide useful insights for the design of activatable NIR-II PA probes for precise cancer imaging and therapy.