Sulourea-coordinated Pd nanocubes for NIR-responsive photothermal/H(2)S therapy of cancer

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 ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-021-01042-9.