Ultrathin Metal-Organic Framework as an Allosteric Regulator for Albumin-Responsive Therapy of Diabetic Infections.

Customizing sense-and-respond programs that link natural actuations with user-defined cues has emerged as a promising strategy for modulating life processes. Herein, a metal-organic framework (MOF)-based synthetic receptor system is presented for realizing customized biological functions using write-in signaling gates. This is achieved by integrating glucose oxidase into a series of engineered Zr-MOF nanosheets. Notably, ultrathin MOF architectures act as synthetic allosteric regulators by reshaping the interaction network at the enzyme-dimer interface, thus compromising electron-transfer efficiency during catalysis. Leveraging this mechanism, activity modulation is achieved by converting an endogenous yet functionally irrelevant protein, serum albumin, into an activating cue for enzymatic catalysis. This MOF-enzyme system with an albumin/glucose dual-gated output behavior exhibits effective antibacterial activity through kinetically controlled oxidative stress. The therapeutic efficacy is demonstrated in a diabetic wound-healing model. These findings establish MOFs as versatile modules for constructing synthetic receptor systems to advance their use in precision biomedicine.