Sulfate-reducing bacteria loaded in hydrogel as a long-lasting H2S factory for tumor therapy

The continuous supply of hydrogen sulfide (H 2 S) 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 H 2 S-producing donor hampers its extensive application. Sulfate-reducing bacteria (SRB) can serve as an excellent H 2 S factory due to their ability to metabolize sulfate into H 2 S. Herein, a novel injectable chondroitin sulfate (ChS) hydrogel loaded with SRB ( [email protected] Gel) is proposed to sustainably produce H 2 S in tumor tissues to overcome the limitations of current H 2 S 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 H 2 S for at least 7 days, resulting in mitochondrial damage and immunogenic cell death . Once injected into tumor tissue, the [email protected] Gel can constantly produce H 2 S 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 [email protected] Gel, as a safe and long-term, self-sustained H 2 S-generating factory, provides a promising strategy for anti-tumor therapy.