FeS-based cascade bioreactors driven by Shewanella oneidensis MR-1 for efficient chemodynamic therapy with augmented antitumor immunity

Abstract

Chemodynamic therapy (CDT) is an emerging therapeutic approach, which can trigger immune responses by causing tumor cell death and releasing tumor-associated antigens. However, CDT alone is not effective in eliciting a robust immune response. Herein, FeS nanoparticles are in situ fabricated on the surface of Shewanella oneidensis MR-1 (FeS@MR-1) for enhanced CDT to boost antitumor immunity. Under acidic conditions, FeS@MR-1 degrades and simultaneously induces the release of Fe(II) ions and H2S gas. The released H2S can inhibit the activity of catalase, resulting in the accumulation of H2O2, which facilitates the production of highly toxic hydroxyl radical (·OH) through the Fenton reaction catalyzed by Fe(II). Thanks to the iron-reducing ability during the anaerobic respiration process, S. oneidensis MR-1 drives the Fenton reaction to proceed continuously by promoting Fe(III) to Fe(II) conversion to ensure the high efficiency of CDT. Furthermore, FeS@MR-1 can reprogram the immunosuppressive tumor microenvironment by consuming lactate and act as a natural immune adjuvant to enhance immune responses. More importantly, the combined treatment of FeS@MR-1 with immune checkpoint blockade triggers systemic antitumor responses, leading to excellent therapeutic performance against primary, distant, and orthotopic ovarian tumors. This work presents a cascade bioreactor based on S. oneidensis MR-1, which is promising for enhanced CDT and immunotherapy.