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

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.