Photoactivated in-situ engineered-bacteria as an efficient H₂S generator to enhance photodynamic immunotherapy via remodeling the tumor microenvironment.

Abstract

Based on the unique biological advantages of bacteria and their derivatives, biosynthetic nanomaterials have been widely used in the field of tumor therapy. Although conventional bacterial treatments demonstrate potential in activating tumor immunity, their efficacy in inhibiting tumor growth remains constrained. In this study, a photoactivated hydrogen sulfide (H₂S) generator was successfully prepared by in-situ engineering of bacteria, after Pt/MoS₂ nanocomposites were in-situ generated by Escherichia coli (E. coli) and loaded with photosensitizer Ce6. This engineered-bacteria has been proved to have good tumor targeting ability and can enhance the effect of photodynamic therapy in the hypoxic tumor microenvironment. While reactive oxygen species (ROS) is effectively released, the fragmentation of bacteria can accelerate the release of abundant H₂S, and promote tumor-specific H₂S gas therapy, which can effectively remodel the tumor microenvironment and promote the activation of anti-tumor immunotherapy. This engineered bacteria not only improves the tumor specificity and effectiveness of H₂S treatment, but also provides a new idea for nanomaterials in bacterial-mediated synergistic cancer treatment.