Biofilm Microenvironment-Sensitive Piezoelectric Nanomotors for Enhanced Penetration and ROS/NO Synergistic Bacterial Elimination

Sonodynamic therapy offers a highly accurate treatment for bacterial infections; however, its antibacterial efficacy is hindered by bacterial biofilms that limit the penetration of sonosensitizers. Herein, a nitric oxide (NO)-driven mushroom-like Janus nanomotor (BT@PDA-La) based on the unilateral coating of polydopamine (PDA) on piezoelectric tetragonal barium titanate (BT) and further modified with l-arginine (l-Arg) on the PDA side is fabricated. In the infected microenvironment with high levels of H₂O₂, NO is produced unilaterally from BT@PDA-La, thus leading to its self-propelled movement and facilitating its permeability in the biofilm. Under ultrasonic vibrations, the piezoelectric effect of BT@PDA-La is triggered by the exogenous mechanical wave, and toxic reactive oxygen species (ROS) are efficiently generated via an in situ catalytic reaction. The synergistic treatment with ROS/NO achieved the destruction of biofilms and embedded drug-resistant bacteria in vitro. Importantly, BT@PDA-La exhibits excellent biofilm penetration capacity, effectively eliminating biofilm infection while accelerating the healing of infected muscles by alleviating oxidative stress, regulating inflammatory factors, and accelerating angiogenesis. Collectively, this study provides a promising strategy for enhancing the penetration of pathological environment-driven nanomaterials through biofilms and advances the application of nanomotors for the therapy of bacterial infections in clinical medicine.