In Situ Study of Electron-Tunneling through Dynamic Interface at Individual Nanoemulsions by Multimodal Single-Entity Electrochemistry

To overcome critical challenges in modern drug delivery, lipid nanocarriers such as nanoemulsions (NEs) have emerged as superior drug carriers. While advancements in nanotechnology allow precise control over NE size and structure, the rational design of their functionality remains difficult. This is because functionality is primarily dominated by dynamically or statically formed interfacial structures that cannot be easily characterized using ex situ bulk analysis or electron microscopy. Herein, we demonstrate multimodal single-entity electrochemistry (MSEE)─combining amperometric SEE with voltammetry─to in situ probe electron-tunneling through the dynamic interfaces of intact, individual NEs. Using highly monodisperse NEs synthesized with varying concentrations of Pluronic block copolymer surfactants, we investigated interfacial electron transfer (ET) rates at discrete NEs. Notably, ET through the NE interface aligns with the predictions of the Marcus–Hush theory. We determined the effective interfacial thickness, tunneling-distance decay constant, ET rate constants, and transfer coefficient. This enabled angstrom-resolution differentiation of interfacial structures and structure-dependent charge-transfer behaviors across a series of NEs, independent of morphological size differences. Our MSEE approach provides a powerful electrochemical framework for investigating nanostructure–function relationships in lipid nanocarriers with mixed interfacial layers, ultimately aiding in the optimization of desired functionality such as delivery efficiency, release kinetics, and carrier stability.