Redox-Activatable and Acid-Enhanced Nanotheranostics for Second Near-Infrared Photoacoustic Tomography and Combined Photothermal Tumor Therapy.

Tumor phototheranostics in the second near-infrared window (NIR-II, 1000-1700 nm) holds great promise due to high spatiotemporal precision, enhanced penetration depth, and therapeutic efficacy. However, current "always-on" NIR-II phototheranostic agents remain restricted by the inherent nonspecificity from the pseudosignal readout and undesirable treatment-related side effects. To address these challenges, herein we explore an activatable and biocompatible nanotheranostics that generates diagnostic and therapeutic effects only after specific activation and enhancement by tumor microenvironmental redox and acid while keeping silent at normal tissues. Such an intelligent "turn-on" chromogenic nanotheranostics allows in vivo nearly zero-background photoacoustic tomography (PAT) and combined effective photothermal tumor therapy (PTT) both in the NIR-II range with minimal adverse effects. In light of the high sensitivity, superior penetration depth, and biocompatibility, this stimuli-activatable NIR-II photo-nanotheranostics provides broad prospects for the investigation and intervention of deep-tissue redox and acid-associated physiological and pathological events.