Microenvironment-responsive nanomotors enable enhanced biofilm penetration and immune reprogramming for peri-implantitis therapy

BACKGROUND: Peri-implantitis is driven by persistent multispecies biofilms and a pathological inflammatory microenvironment characterized by elevated reactive oxygen species (ROS), acidic pH, and sustained pro-inflammatory macrophage activation. These coupled features severely limit the efficacy of conventional antimicrobial therapies by restricting drug penetration into mature biofilms and perpetuating immune dysregulation. Therapeutic strategies capable of simultaneously overcoming biofilm mass-transport barriers and restoring immune homeostasis remain lacking. RESULTS: Herein, we report a microenvironment-responsive nanomotor system (M-CaO₂-CL) that converts pathological inflammatory cues into sustained autonomous motion, enabling active biofilm penetration and concurrent immunomodulation. Triggered by elevated hydrogen peroxide (H₂O₂) and sustained by acidic pH, the nanomotors generate continuous oxygen-driven propulsion, facilitating deep infiltration into dense biofilm matrices and overcoming diffusion-limited transport. This motion-enabled behavior markedly enhances antibacterial efficacy, particularly when combined with mild photothermal treatment under near-infrared irradiation (< 48 °C), achieving efficient biofilm disruption without detectable collateral tissue damage. Beyond antibiofilm activity, the nanomotor platform exhibits intrinsic antioxidant and anti-inflammatory functions, effectively scavenging excessive ROS and reprogramming macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype. In a rat peri-implantitis model, M-CaO₂-CL treatment significantly reduced bacterial burden, suppressed pro-inflammatory cytokine expression, and preserved peri-implant bone architecture. CONCLUSIONS: Collectively, this study demonstrates a multifunctional nanomotor-based therapeutic strategy that integrates inflammation-responsive propulsion, enhanced biofilm penetration, mild photothermal disinfection, and immune reprogramming. By harnessing pathological microenvironmental cues as endogenous driving forces, the M-CaO₂-CL nanomotor effectively addresses key biological barriers in peri-implantitis, establishing a promising nanotherapeutic platform for biofilm-associated inflammatory diseases.