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Macrotheranostic Probe with Disease-Activated Near-Infrared Fluorescence, Photoacoustic, and Photothermal Signals for Imaging-Guided Therapy.

Theranostics provides opportunities for precision cancer therapy. However, theranostic probes that simultaneously turn on their diagnostic signal and pharmacological action only in respond to a targeted biomarker have been less exploited. We herein report the synthesis of a macrotheranostic probe that specifically activates its near-infrared fluorescence (NIRF), photoacoustic (PA), and photothermal signals in the presence of a cancer-overexpressed enzyme for imaging-guided cancer therapy. Superior to the small-molecule counterpart probe, the macrotheranostic probe has ideal biodistribution and renal clearance, permitting passive targeting of tumors, in situ activation of multimodal signals, and effective photothermal ablation. Our study thus provides a macromolecular approach towards activatable multimodal phototheranostics.