NIR-IIb-triggered microbial upconversion photosynthesis enables hypoxia-resistant tumor lactate catabolism

Elevated lactate levels in solid tumors contribute to immunosuppression, metabolic reprogramming, and resistance to therapy. Although lactate oxidase (LOX) offers a viable strategy for in situ lactate depletion, its therapeutic efficacy is fundamentally limited by tumor hypoxia due to the oxygen dependence of LOX. Here, we report a hybrid nanomaterial-microbial system that enables hypoxia-resistant lactate catabolism through near-infrared (NIR)-IIb-triggered upconverson photosynthesis. This system integrates LOX-producing Escherichia coli (E. coli) with Chlorella (Chl) and lanthanide-doped upconversion nanoparticles (UCNPs), which convert deeply penetrating 1550 nm light into visible emission to drive oxygenic photosynthesis. Unlike conventional photosynthetic oxygenation approaches limited by shallow visible light penetration, this system enables spatiotemporally controlled oxygen generation deep within tumors, sustaining LOX activity under hypoxia. In murine tumor models, the hybrid symbionts significantly inhibited tumor growth, promoted T cell infiltration, and induced durable immune memory. This work establishes a versatile optogenetic-metabolic platform for overcoming oxygen-limited metabolism in cancer therapy via deep-tissue-activatable microbial photosynthesis.