In vivo electrochemical reduction-induced reconfiguration of Prussian blue for metal counterion-free potassium removal in hyperkalemia.

Abstract

Hyperkalemia, a life-threatening metabolic disorder, persists as unmet medical need since current first-line pharmacotherapy-ion-exchange potassium binders-inevitably release metal counterions (e.g., sodium) that paradoxically aggravate metabolic comorbidities. Here, we present a paradigm-shifting in vivo reduction-induced ion-selective adsorption (IRISA) strategy, utilizing Prussian Blue and Vitamin C for metal counterion-free potassium removal. IRISA leverages VC to trigger structural remodeling of PB through Fe reduction, inducing spin-state transitions and lattice reconfiguration that create K-specific channels with optimized charge distribution. Spectroscopic studies and DFT calculations reveal Kadsorption through electron density redistribution at coordinatively unsaturated Fe sites. This ion adsorption mechanism enables selective adsorption of Kwithout metal counterion release. In three male animal models of hyperkalemia, it rapidly normalizes serum Kwhile preserving Nahomeostasis, offering a critical advantage over current first-line therapies that perturb sodium balance. Our findings establish a new paradigm for electrolyte disorder treatment using in vivo reduction-induced material reconfiguration, merging electrochemical principles with precision medicine.