Near-Infrared Light-Propelled MOF@Au Nanomotors for Enhanced Penetration and Sonodynamic Therapy of Bacterial Biofilms

Sonodynamic therapy (SDT) utilizes ultrasound (US) to activate sonosensitizers to generate highly cytotoxic reactive oxide species (ROS), which has achieved great success in eradicating deep-seated bacterial infections. However, the limited penetration and low diffusion efficacy of sonosensitizers in biofilms severely impair the therapeutic effects of SDT. Herein, we design a near-infrared (NIR) light-driven nanomotor (MOF@Au-DNase I) with high electron–hole pairs separation efficiency for combating Staphylococcus aureus (S. aureus) biofilms. Specifically, gold nanoparticles (Au NPs) are deposited onto one-half of the sphere-shaped metal–organic framework (MOF) to construct Janus MOF@Au NPs, followed by the covalent immobilization of deoxyribonuclease (DNase I) onto the surface of MOF@Au. Under the NIR laser irradiation, MOF@Au NPs exhibit efficient active motion and penetrated quickly into deep biofilms within 15 min. Notably, DNase I can destroy the compactness of biofilms by hydrolyzing extracellular DNA (eDNA) in biofilms to facilitate the penetration of sonosensitizers. Moreover, the asymmetric spatial distribution of Au can significantly improve the electron transfer efficiency of MOF@Au and finally enhance the ROS generation. The synergistic effect enhances the efficiency of SDT-mediated therapy of the Janus MOF@Au NPs. The high ROS generation capacity of MOF@Au-DNase I realizes superior bactericidal effects in vitro and accelerates the healing process of biofilm-infected cutaneous wounds in vivo, demonstrating a flexible and effective strategy for biofilm eradication.