1. Journal Source: Biomaterials

2. Original Title: An allosteric reconfigurable metabzyme hydrogel for adaptive tumor metabolic immunotherapy

3. Research Highlights: Inspired by the enzyme-induced fit catalytic mechanism, this work designs an allosteric reconfigurable metabzyme hydrogel. A manganese-doped molybdenum oxide metabzyme is constructed to realize NADH-triggered interfacial lattice reconfiguration. Combined with small-molecule herbal compounds, it forms a thermosensitive chitosan hydrogel that modulates tumor metabolic reprogramming and activates the cGAS‑STING pathway. The mechanism underlying its inhibition of tumor recurrence is investigated.

4. Innovations: A substrate-triggered allosteric reconfiguration strategy is proposed. High-entropy distorted lattices enable coupled proton-electron transfer, breaking the limitations of conventional static nanozyme interfacial catalysis. The metabzyme and small-molecule drugs are co-encapsulated within thermosensitive hydrogels for hierarchical release, enabling simultaneous metabolic intervention and immune signal activation. The synergistic activation of cGAS‑STING via multiple pathways including the NADH‑lactate axis, metal ions and reactive oxygen species is elucidated, and the contribution weight of each pathway is analyzed.

5. Material Development (1) Materials: Manganese-doped molybdenum oxide metabzyme (Mn‑MoOₓ), which is integrated with bergenin A to fabricate thermosensitive chitosan-based RMnG hydrogel. (2) Functions: It undergoes lattice reconfiguration in response to substrates and exhibits multiple enzyme-mimicking catalytic activities. It can form hydrogels in situ, reprogram tumor glycolysis, relieve lactylation-mediated inhibition of cGAS, and activate anti-tumor innate immunity.

6. Extended Perspective: This substrate-responsive allosteric catalysis paradigm can be extended to more biomimetic catalysts, offering design principles for developing hydrogel materials with synergistic metabolic-immune regulation.

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