Molecular Trojan Based on Membrane-Mimicking Conjugated Electrolyte for Stimuli-Responsive Drug Release

Abstract

Enhancing payload encapsulation stability while enabling controlled drug release are both critical objectives in drug delivery systems but are challenging to reconcile. This study introduces a zwitterionic conjugated electrolyte (CE) molecule named Zwit, which acts as a molecular Trojan by mimicking the lipid bilayers. When integrated into liposome membranes, Zwit rigidifies the bilayer structure likely due to its hydrophobic interactions providing structural support, thus inhibiting drug leakage. Upon 808 nm laser excitation, Zwit rapidly accelerates DOX release from liposome core, likely due to light-triggered conformational changes or photothermal effects that compromise membrane permeability. These findings demonstrate Zwit’s ability to overcome the challenge of simultaneously preventing premature payload leakage and enabling stimuli-responsive drug release with a single component. Additionally, Zwit exhibits excellent biocompatibility with membranes, outperforming its quaternary ammonium counterpart and commonly used dye indocyanine green (ICG). By harnessing its NIR-II emission, Zwit enables durable in vivo biodistribution tracking of nanocarriers, whereas ICG suffers from significant dye leakage. In subcutaneous tumor models, the synergistic effects of chemotherapy and thermotherapy facilitated by this light-triggered system induced a potent antitumor immune response, further enhancing anticancer efficacy. This work underscores the potential of membrane-mimicking CEs as multifunctional tools in advanced drug delivery systems.