Acid‐Responsive Bacteria‐Targeted Zinc‐Porphyrin Based Sonosensitizer with Enhancing Antibacterial Efficacy and Biofilm Eradication for Infected Wounds Healing

Abstract Diseases caused by bacterial infections place a significant burden on global public health. Sonodynamic therapy (SDT), as an emerging antibacterial treatment, faces clinical challenges due to the non‐polar nature of most sonosensitizers. To address this, an acid‐responsive zinc‐porphyrin‐based sonosensitizer (Zn‐TCPP) is developed via a simple thermal reaction, which is then coated with phenylboronic acid‐modified hyaluronic acid (B‐HA), to fabricate B‐HA@Zn‐TCPP. While in the mildly acidic microenvironment mimicking an infected wound site, the released B‐HA@Zn‐TCPP achieves effective SDT activity. The disruption of the bacterial membrane and the levels of intracellular reactive oxygen species (ROS) verified that the inhibition rate can reach 99% within 5 min, without any development of resistance after 15 consecutive generations of culture. Additionally, under ultrasound (US) ‐mediated cavitation, B‐HA@Zn‐TCPP exhibits excellent penetration into biofilms, achieving a 90.04% bactericidal rate for bacteria within biofilms. In vivo studies further demonstrated that B‐HA@Zn‐TCPP can effectively accelerate the healing of bacterial infected wounds with a wound healing rate of 98.65% within 9 days. Therefore, B‐HA@Zn‐TCPP as a novel sonosensitizer offers a viable strategy to overcome the limitations of traditional sonosensitizers for the bacterial wound infections.