Ros-sensitive hydrogel system incorporating mitochondria-targeted liposomes for periodontitis treatment

Schematic illustration of CoQ10-MLip/Gel and its mechanism diagram for the periodontal treatment. Created with BioRender.com . • ROS-sensitive hydrogel with CoQ10-MLip/Gel enhances CoQ10 bioavailability and mitochondrial targeting. • Dual-action ROS control: scavenge extracellular ROS and reduce mitochondrial ROS production. • Mechanism-based periodontitis therapy: ROS regulation, mitochondrial repair and immune modulation. Periodontitis, the sixth most prevalent human disease, involves excessive ROS and mitochondrial dysfunction as key pathological drivers. However, therapeutic strategies simultaneously targeting both mechanisms for optimal regeneration remain scarce. To address this, we developed a ROS-responsive hydrogel (Gel) integrated with mitochondria-targeted liposomes encapsulating Coenzyme Q10 (CoQ10-MLip/Gel). The CoQ10-MLip combines CoQ10 (mitochondrial electron carrier) with arginine residues (mitochondrial-targeting motifs). The phenylboronic ester-based Gel degrades under high ROS, enabling controlled CoQ10-MLip release. Its self-healing properties and injectability ensure prolonged retention in periodontal pockets. This system effectively eliminated ROS, restored mitochondrial integrity, and significantly mitigated periodontal inflammation in vivo. The CoQ10-MLip/Gel platform thus offers a promising strategy for periodontitis treatment and potentially other chronic inflammatory diseases.