G-Quadruplex Hydrogel-Based Stimuli-Responsive High-Internal-Phase Emulsion Scaffold for Biocatalytic Cascades and Synergistic Antimicrobial Activity

High-internal-phase emulsions (HIPEs) are nonequilibrium systems with distorted liquid droplet shapes consisting of a high volume of the internal phase (>74% v/v), enabling a high loading of pharmaceutics and useful viscoelastic properties. However, HIPEs are inherently unstable and require a substantial amount of surfactants in the continuous phase for long-term stability, making it environmentally unfriendly. Utilization of hydrogel as the continuous phase to stabilize HIPEs would offer a robust method to produce stable HIPE gels displaying reconfigurable and biocompatible properties, as well as access the huge repertoire of different biocompatible hydrogels. Herein, we introduce a new gel-immobilized HIPE (HIPEG) using chiral G-quadruplex (GQ)-based hydrogel with external stimuli-responsive dual-drug release behavior, which is scarce for HIPEs. The hydrophilic and hydrophobic compartments of the biocompatible HIPEG allow encapsulation of different drugs in both the compartments, with stimuli-responsive diffusion-mediated release. Encapsulation of natural oils and antibiotics produces synergistic antimicrobial effects on both Gram-positive (MRSA) and Gram-negative (Pseudomonas aeruginosa) bacterial strains through increased oxidative stress and membrane depolarization. Moreover, we demonstrate biocatalytic reaction networks utilizing compartmentalized enzyme dyads. Notably, the ideal viscoelastic property of HIPEGs enables 3D printing of different shapes, making the scaffold suitable for the creation of soft medical devices. Altogether, our approach provides a one-step route to creating stimuli-responsive HIPE microcompartments immobilized in GQ hydrogels with endogenous reactivity and high viscoelasticity, offering a viable step toward the development of biocompatible soft materials with tailorable functionality.