Vesicle-confined redox mediation via biomimetic ABTS-liposomes enables stable electron relay and dual-mode H₂O₂...

Uncontrolled diffusion and instability of redox mediators remain major challenges limiting the durability and fidelity of electrochemical biosensors. Here, we report a biomimetic strategy that encapsulates 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) within phospholipid vesicles to construct a vesicle-confined electron relay platform for hydrogen peroxide (H₂O₂) sensing. The confined aqueous microenvironment preserves the redox activity of ABTS, prevents mediator leakage and degradation, and enables efficient electron shuttling with horseradish peroxidase (HRP). Consequently, the biosensor achieves ultrasensitive electrochemical detection (LOD: 2.53 nM), retains >70 % of its activity after 30 days at 4 °C, and endures over 500 CV cycles without signal loss. In parallel, a complementary chromogenic output provides an intuitive visual response in the micromolar range, underscoring the synergistic advantages of recyclable electrochemical relays versus one-off colorimetric products. Importantly, the platform enabled intracellular H₂O₂ monitoring in living cells, validating its biocompatibility and robustness under biologically relevant conditions. This organelle-inspired, dual-mode sensing architecture offers a generalizable framework for stabilizing redox mediators through nanoconfinement and opens new avenues for durable, field-deployable point-of-care biosensing.