Amplified copper ion interference and immunomodulation using self-thermophoretic nanomotors to treat refractory implant-associated biofilm infections

Orthopedic implant-associated biofilm infections (IABIs) are refractory to elimination because of the dense biofilm formation and local immunosuppressive microenvironment. Herein, we propose a copper-based therapeutic strategy to treat IABIs. Initially, the Janus bisphere nanostructure is fabricated using mesoporous silicon nanoparticle (MSN) with gold nanoparticle. Subsequently, copper peroxide (CP) nanodots are encapsulated within the MSN to form the final nanomotor Motor@CP. Our Motor@CP exhibits remarkable autonomous movement through near-infrared (NIR)-propelled self-thermophoretic propulsion, effectively penetrating dense biofilms and delivering CP. Notably, the acidic microenvironment facilitates CP decomposition into copper(II) and hydrogen peroxide. This process further generates hydroxyl radicals (•OH), extensively destroying biofilm integrity and enhancing intracellular uptake of copper ions that trigger bacterial cuproptosis-like death. Furthermore, Motor@CP markedly reprograms infiltrating macrophages toward pro-inflammatory phenotypes, thereby promoting an antimicrobial immune response. Overall, this presents a promising approach that leverages amplified copper ion interference and macrophage reprogramming to combat refractory orthopedic IABIs.