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Background  Photothermal therapy (PTT) frequently cause thermal resistance in tumor cells by inducing the heat shock response, limiting its therapeutic effect. Hydrogen sulfide (H 2 S) with appropriate concentration can reverse the Warburg effect in cancer cells. The combination of PTT with H 2 S gas therapy is expected to achieve synergistic tumor treatment.    Methods  Here, sulourea (Su) is developed as a thermosensitive/hydrolysable H 2 S donor to be loaded into Pd nanocubes through in-depth coordination for construction of the Pd-Su nanomedicine for the first time to achieve photo-controlled H 2 S release, realizing the effective combination of photothermal therapy and H 2 S gas therapy.    Results  The Pd-Su nanomedicine shows a high Su loading capacity (85 mg g −1 ), a high near-infrared (NIR) photothermal conversion efficiency (69.4%), and NIR-controlled H 2 S release by the photothermal-triggered hydrolysis of Su. The combination of photothermal heating and H 2 S produces a strong synergetic effect by H 2 S-induced inhibition of heat shock response, thereby effectively inhibiting tumor growth. Moreover, high intratumoral accumulation of the Pd-Su nanomedicine after intravenous injection also enables photothermal/photoacoustic dual-mode imaging-guided tumor treatment.    Conclusions  The proposed NIR-responsive heat/H 2 S release strategy provides a new approach for effective cancer therapy.    Graphic abstractSupplementary Information  The online version contains supplementary material available at 10.1186/s12951-021-01042-9.

Sulourea-coordinated Pd nanocubes for NIR-responsive photothermal/H2S therapy of cancer