Electrically and redox-responsive PEDOT/waterborne polyurethane membranes for controlled delivery of a tumor-homing peptide

Stimuli-responsive biomaterials that integrate endogenous and externally addressable triggers offer advanced opportunities for controlled and localized delivery of therapeutic biomolecules. In this study, we present the fabrication and characterization of hierarchical conductive membranes based on poly(3,4-ethylenedioxythiophene) (PEDOT) and a redox-responsive waterborne polyurethane (WPU), functionalized with the tumor-homing peptide CREKA. A stepwise electropolymerization strategy was employed to generate a compact PEDOT base layer followed by a PEDOT/CREKA composite layer, while a glutathione-responsive WPU topcoat provided mechanical compliance and an additional peptide reservoir. The resulting membranes exhibited high water uptake (approximately 1.85 X) and long-term hydrolytic stability up to 90 days. Atomic force microscopy revealed mechanically heterogeneous surfaces, with compliant WPU domains overlaying rigid, conductive PEDOT layers. Electrochemical analysis demonstrated preserved PEDOT redox activity and enhanced cycling stability (≈3% loss of electroactive charge after 200 cyclic voltammetry cycles), while the formation of an additional capacitive interface upon peptide incorporation resulted in tunable interfacial charge storage and polymer-peptide interactions. Moreover, the integration of an electroactive PEDOT phase with a redox-responsive WPU matrix enabled the precise modulation of peptide release through complementary electrical and biochemical triggers. Overall, this membrane-based architecture enables the controlled peptide delivery at soft biointerfaces, being especially relevant for localized cancer-related applications and electrically addressable biomaterial systems.