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

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 K⁺ adsorption through electron density redistribution at coordinatively unsaturated Fe sites. This ion adsorption mechanism enables selective adsorption of K⁺ without metal counterion release. In three male animal models of hyperkalemia, it rapidly normalizes serum K⁺ while preserving Na⁺ homeostasis, 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.