An Activatable Phototheranostic Nanoplatform for Tumor Specific NIR‐II Fluorescence Imaging and Synergistic NIR‐II Photothermal‐Chemodynamic Therapy

The phototheranostics in the second near‐infrared window (NIR‐II) have proven to be promising for the precise cancer theranostics. However, the non‐responsive and “always on” imaging mode lacks the selectivity, leading to the poor diagnosis specificity. Herein, a tumor microenvironment (TME) activated NIR‐II phototheranostic nanoplatform (Ag2S‐Fe(III)‐DBZ Pdots, AFD NPs) is designed based on the principle of Förster resonance energy transfer (FRET). The AFD NPs are fabricated through self‐assembly of Ag2S QDs (NIR‐II fluorescence probe) and ultra‐small semiconductor polymer dots (DBZ Pdots, NIR‐II fluorescence quencher) utilizing Fe(III) as coordination nodes. In normal tissues, the AFD NPs maintain in “off” state, due to the FRET between Ag2S QDs and DBZ Pdots. However, the NIR‐II fluorescence signal of AFD NPs can be rapidly “turn on” by the overexpressed GSH in tumor tissues, achieving a superior tumor‐to‐normal tissue (T/NT) signal ratio. Moreover, the released Pdots and reduced Fe(II) ions provide NIR‐II photothermal therapy (PTT) and chemodynamic therapy (CDT), respectively. The GSH depletion and NIR‐II PTT effect further aggravate CDT mediated oxidative damage toward tumors, achieving the synergistic anti‐tumor therapeutic effect. The work provides a promising strategy for the development of TME activated NIR‐II phototheranostic nanoprobes. A tumor microenvironment (TME) activated second near‐infrared window (NIR‐II) phototheranostic nanoplatform is successfully fabricated via the coordination self‐assembly. NIR‐II fluorescence signals of the self‐assembly could be responsively “turn on” by overexpressed GSH in TME for tumor‐specific diagnosis, simultaneously achieving NIR‐II imaging guided synergistic NIR‐II photothermal‐chemodynamic therapy.