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 anti-tumor 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, self-sustained H₂S-generating factory, provides a promising strategy for anti-tumor therapy.