AIE Photosensitizer with Tuned Membrane Interactions for Effective-Gram-Negative Bacteria Elimination

Photodynamic antimicrobial therapy (PDAT) for efficient bacterial infection eradication critically relies on photosensitizers (PSs) that can specifically target and disrupt bacterial membranes. However, the complex membrane architecture of Gram-negative bacteria poses a significant challenge to the efficacy of most aggregation-induced emission (AIE) PSs. Herein, we introduce TPQ, an AIE PS meticulously designed to overcome this challenge by incorporating an outer membrane disruption ability, thereby boosting PDAT efficacy against Gram-negative bacteria. TPQ demonstrated excellent microbial imaging and potent PDAT activity against both Gram-positive and Gram-negative bacteria, attributed to its inherent fluorescence, high singlet oxygen generation, and balanced electrostatic and hydrophobic interactions with bacterial membranes. Notably, TPQ achieved exceptional PDAT activity (>97% efficacy) against Gram-negative bacteria while exhibiting minimal cytotoxicity to mammalian cells. Furthermore, TPQ-mediated PDAT effectively healed <i>Escherichia coli</i>-infected wounds on mice models with assured biosafety. This work provides valuable insights into the rational design of AIE PSs and highlights the synergistic effect of membrane disruption for advancing PDAT applications, particularly against recalcitrant Gram-negative bacterial infections.