Ultrasound‐Actuated Tissue Remodeling Integrates Living Bacterial Sonosensitization for Enhanced Tumor Therapy

ABSTRACT Sonodynamic therapy (SDT) is a promising non‐invasive modality for treating deep‐seated tumors, yet its efficacy remains constrained by the poor tumor accumulation of conventional sonosensitizers. To address this, we developed a bacteria‐based SDT strategy employing Rhodopseudomonas palustris (R.P) as a self‐propelled, living sonosensitizer that leverages inherent hypoxia tropism and active motility. Our results suggest that bacteriochlorophyll embedded in the bacterial membrane could act as an effective sonosensitizer, generating reactive oxygen species (ROS) upon ultrasound stimulation and contributing to tumor cell killing via sonochemical effects. Notably, ultrasound also exerts a mechanical effect, inducing approximately 1.35‐fold dilation of tumor vessels. Molecular dynamics simulations indicate that periodic ultrasound forces may cause reversible deformation of cell membranes, characterized by transient expansion of intermolecular spacing and rapid structural stretching. This ultrasound‐mediated tissue remodeling might enhance tumor permeability, potentially facilitate deeper bacterial infiltration, and contributing to the improved efficacy of SDT. Together, these results present a bacteria‐based SDT approach that integrates living therapeutics with self‐propulsion and physical actuation, offering a potential strategy to expand the therapeutic scope of ultrasound in cancer treatment.