Living therapeutics of nonpathogenic bacteria as biosynthesis factory and active carriers for enhancing tumor-targeted therapy

Anaerobic bacteria-mediated tumor therapy faces multiple challenges, including potential toxic side effects, complex manufacturing processes, and impaired hypoxic targeting. Here, based on the excellent biocompatibility and distinctive metabolic ability of natural anaerobic sulfate-reducing bacteria (SRB) to dissimilate sulfate into sulfide, we construct in situ-biosynthesized ferrous sulfide nanoparticle-SRB (FeS@SRB) biohybrid to enhance tumor-targeted therapy. Interestingly, SRB acts as both a biosynthesis factory and active tumor-targeted delivery vehicles. Our systematic studies reveal that FeS@SRB has excellent biosafety and tumor targeting capabilities, achieving over 50% tumor delivery efficiency in female mice post-intravenous injection, which is 17 times higher than that of conventional chemically-synthesized FeS@BSA nanoparticles. Upon near-infrared laser irradiation, FeS@SRB hybrids exhibit synergistic photothermal-chemodynamic effect, amplifying oxidative stress to trigger tumor cells ferroptosis and apoptosis, thereby effectively suppressing both subcutaneous and orthotopic tumor growth. This SRB-based therapeutic strategy expands research into tumor-targeting platforms and the biosynthesis of metal sulfide nanoparticles for enhanced tumor therapy.