Ultrathin Metal–Organic Framework as an Allosteric Regulator for Albumin‐Responsive Therapy of Diabetic Infections

Abstract

ABSTRACT 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.