Sulfate-reducing Bacteria Loaded in Hydrogel As a Long-Lasting H2S Factory for Tumor Therapy.

The continuous supply of hydrogen sulfide (H2S) gas at high concentrations to tumors is considered a promising and safe strategy for tumor therapy. However, the absence of a durable and cost-effective H2S-producing donor hampers its extensive application. Sulfate-reducing bacteria (SRB) can serve as an excellent H2S factory due to their ability to metabolize sulfate into H2S. Herein, a novel injectable chondroitin sulfate (ChS) hydrogel loaded with SRB (SRB@ChS Gel) is proposed to sustainably produce H2S in tumor tissues to overcome the limitations of current H2S gas therapy. In vitro, the ChS Gel not only supports the growth of encapsulated SRB, but also supplies a sulfate source to the SRB to produce high concentrations of H2S for at least 7 days, resulting in mitochondrial damage and immunogenic cell death. Once injected into tumor tissue, the SRB@ChS Gel can constantly produce H2S for >5 days, significantly inhibiting tumor growth. Furthermore, such treatment activates systemic antitumor immune responses, suppresses the growth of distant and recurrent tumors, as well as lung metastases, meanwhile with negligible side effects. Therefore, the injectable SRB@ChS Gel, as a safe and long-term, selfsustained H2S-generating factory, provides a promising strategy for anti-tumor therapy.