Hydrogen Sulfide-Specific and NIR-Light-Controllable Synergistic Activation of Fluorescent Theranostic Prodrugs for Imaging-Guided Chemo-Photothermal Cancer Therapy

Theranostic prodrugs are promising for cancer medicine; however, the inability to activate these systems exclusively at the desired tumor location compromises the specificity and efficacy of cancer treatment. Here, we developed a fluorescent theranostic nanoprodrug with synergistic hydrogen-sulfidespecific and near-infrared (NIR)-light-controllable activation for imaging-guided chemo-photothermal cancer therapy. This nanoprodrug system was fabricated by the inclusion of hydrogen sulfide (H2S)activatable small molecule to the theranostic prodrug and a photothermal transducer in the interior of a NIR-light-responsive container. The resultant nanoprodrug could be activated specifically, evidenced by a turn on of NIR fluorescence in H2S-rich cancers; thus, enabling accurate cancer location and identification of when and where to implement NIR irradiation for efficient conversion of photoenergy into heat. Such a prominent photothermal effect guarantees photothermal ablation of cancers and the release of the H2S-preactivated DOX for cancer chemotherapy. By utilizing this H2S-responsive and NIR-light-controllable nanoprodrug, complete suppression of tumors was realized under the guidance of the NIR fluorescence imaging. Thus, our study provides a novel strategy toward theranostic prodrug systems that enable precision cancer treatment with high specificity and efficacy.