The core challenge of H 2 S therapy is to supply H 2 S in a continuous and steady way. By self-polymerizing lipoic acid trisulfide, herein a new H 2 S donor called poly-lipoic acid trisulfide particles (pLATP) is developed with the steady H 2 S supply over 48 h at both cellular and animal levels, the longest time reported so far. Mechanistically, the pLATP high-efficiently enters the cytoplasm via the poly(trisulfides) mediated membrane penetration. In cells, thanks to the polymerized solid sphere structure, the pLATP releases H 2 S by a layer-by-layer decomposed way. Only when the outer layer decomposes, the inner layer can be exposed. After H 2 S release, the pLATP degrades to lipoic acid, which is not only a B vitamin, but also enhances the expression of 3-mercaptopyruvate sulfurtransferase, a H 2 S synthesizing enzyme promoting the production of endogenous H 2 S. The dual pathways of exogenous supplementation and endogenous recovery warrant the continuous and steady supply of H 2 S at the lesion site. As a proof of concept, the pLATP normalized cardiac function in rats with myocardial ischemia-reperfusion injury.
Background Photothermal therapy (PTT) frequently cause thermal resistance in tumor cells by inducing the heat shock response, limiting its therapeutic effect. Hydrogen sulfide (H2S) with appropriate concentration can reverse the Warburg effect in cancer cells. The combination of PTT with H2S gas therapy is expected to achieve synergistic tumor treatment.Methods Here, sulourea (Su) is developed as a thermosensitive/hydrolysable H2S 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 H2S release, realizing the effective combination of photothermal therapy and H2S 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 H2S release by the photothermal-triggered hydrolysis of Su. The combination of photothermal heating and H2S produces a strong synergetic effect by H2S-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.Conclusion sThe proposed NIR-responsive heat/H2S release strategy provides a new approach for effective cancer therapy.Graphic abstract
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