Engineering Bacteria in Hydrogel for Photo-Triggered Metabolic-Regulation AND-Gated Tumor Immunotherapy

Area of Science:

• Biomaterials Science
• Immunotherapy
• Metabolic Engineering

Background:

• Tumor cells alter metabolism and microenvironment for proliferation and metastasis, causing immunosuppression.
• Engineered living materials offer novel therapeutic strategies.
• Targeting tumor metabolism is a key approach in cancer immunotherapy.

Purpose of the Study:

• To construct an AND-gated living hydrogel for metabolic regulation to enhance tumor immunotherapy.
• To investigate the potential of engineered bacteria within a hydrogel system for cancer treatment.

Main Methods:

• Genetically rewiring bacteria to express lactate oxidase or glucose oxidase under thermosensitive control.
• Encapsulating bacteria within a near-infrared (NIR) light-controlled hydrogel.
• Utilizing laser triggers to activate enzyme expression and modulate tumor cell metabolism.

Main Results:

• The hydrogel successfully weakened tumor cell glycolysis and enhanced mitochondrial respiration.
• Metabolic regulation potentiated anti-tumor immune responses, including T cell stimulation and M1 macrophage polarization.
• The system effectively stimulated immunogenic cell death and the cGAS/STING pathway.
• An AND-gated logic system achieved enhanced immunotherapy with dual enzyme input.

Conclusions:

• An AND-gated living hydrogel system for metabolic regulation demonstrates enhanced tumor immunotherapy.
• This approach offers a novel strategy for modulating the tumor microenvironment and boosting anti-tumor immunity.