Photoacoustic (PA) probes absorbing in the second near-infrared (NIR-II: 1000-1700 nm) window hold great promise for deep-tissue diagnosis and treatment. Currently, NIR-II PA probes typically involve complex synthesis and surfactant adjuvant for processing and delivery. Furthermore, these NIR-II PA probes are "always-on," leading to inadequate signal-to-background ratio and low specificity. To address these challenges, this study reports a pH-activatable and aggregation-enhanced NIR-II PA probe. Without using any toxic or exotic oxidants, the selected polymer () is readily doped by oxygen in an ambient environment and simultaneously red-shifts its absorption profile from visible to NIR-II region. By virtue of the carboxyl groups on the side chains, oxygen-doped is readily water-soluble at a physiological pH but tends to aggregate in an acidic environment. The pH-induced aggregation results in a significant PA enhancement and thus allows specific PA imaging of acidic tumor microenvironment . Our study provides a facile and surfactant-free strategy for achieving water-soluble and pH-responsive NIR-II PA probes, which could be applied for diagnoses of cancer and other diseases associated with changes in pH. It paves the way for the development of new activatable NIR-II imaging probes and also could facilitate the investigation of biological and pathological processes in deep tissue.
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