From Spark to Flame: ROS- and Light-Cascade Activatable NIR-II AIE Probe for Precise Tumor Imaging and Self-Amplifying Phototherapy.

The development of photoactivatable theranostic probes represents a major focus in precision tumor therapy. However, those previously reported probes often suffer from limited photoresponsivity, short excitation/emission wavelengths, and inactivity in the absence of light, restricting their ability to precisely diagnose deep-seated tumors or enable effective phototherapy without auxiliary interventions. To address these challenges, this study designs a second near-infrared (NIR-II) aggregation-induced emission (AIE) theranostic probe based on a dihydroindole skeleton, featuring dual reactive oxygen species (ROS)- and NIR light-cascade activation. Upon ROS activation in the tumor microenvironment, TT-DHIn undergoes transformation into TT-In, exhibiting NIR-II fluorescence emission and photodynamic/photothermal therapy (PDT/PTT) capabilities, thereby serving as a photoactivatable "guiding radar" with an exceptional signal-to-background ratio. Following pre-activation, TT-In efficiently generates ROS under 660 nm laser irradiation, enabling self-supplementation of intratumor ROS. Furthermore, the intratumor TT-DHIn undergoes cyclic conversion into TT-In, significantly enhancing phototherapeutic efficacy and demonstrating potent in vitro cytotoxicity and in vivo tumor eradication. This dual-activatable cascade strategy synergistically integrates tumor biomarker (ROS) responsiveness with photoactivation, offering a promising platform for NIR-II imaging-guided precision phototheranostics with strong potential for clinical translation.