Oxygen-vacancy-rich LDH sonosensitizers potentiate narrow-spectrum antibiotics via membrane-disruption strategy for mixed bacterial wound infections.
- 1Department of Orthopaedics, The First Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, 541001, PR China.
- 2Department of Electrical Engineering, City University of Hong Kong, Hong Kong SAR, PR China.
- 3State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, 100029, PR China.
Abstract
Mixed bacterial infections, including Gram-positive and Gram-negative pathogens, remain a major global health concern. Achieving efficient treatment of synergistic polymicrobial infections stills a tremendous clinical challenge due to antibiotic permeability barriers and resistance. Here, we construct a defect-engineered layered double hydroxide (LDH)-based sonosensitizer platform loaded with clindamycin (a-CoW/CLD) for mixed bacterial infection therapy, which not only demonstrates high efficacy against Gram-positive bacteria, but also exploits reactive oxygen species (ROS)-mediated membrane disruption of Gram-negative bacteria to facilitate CLD penetration, thereby achieving broad-spectrum and highly efficient killing of mixed bacteria. The amorphous a-CoW nanosheets, enriched with oxygen vacancies via acid etching, exhibit a substantially narrowed bandgap (1.22 eV) and markedly enhanced charge separation, producing 22.1-fold higher singlet oxygen under ultrasound (US) irradiation compared with pristine CoW. This ROS burst synergized with CLD achieves potent killing of Staphylococcus aureus (>99.9% at 20 μg mL⁻¹). More critically, ROS disrupt the outer membrane of Gram-negative Escherichia coli, promoting CLD internalization and consequently boosting its lethality by 18.4-fold (from ∼5% to >92.1%). Mechanistic transcriptomics reveals ROS and CLD synergy: ROS disrupt the bacterial membrane via lipid peroxidation, enabling CLD penetration to block protein synthesis and metabolism, while ROS also induce oxidative stress, collectively leading to bacterial death. In a murine wound model co-infected with both pathogens, a-CoW/CLD plus US eradicates >99.9% of mixed bacteria, suppresses systemic inflammation, and significantly accelerates angiogenesis and re-epithelialization. This paradigm establishes a low-dose, broad-spectrum sonodynamic-antibiotic strategy that overcomes antibiotic permeability bottleneck, offering a promising therapeutic avenue against mixed bacterial infections.
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BibTeX
@article{xi2026oxygenvacancyrich,
title = {{Oxygen-vacancy-rich LDH sonosensitizers potentiate narrow-spectrum antibiotics via membrane-disruption strategy for mixed bacterial wound infections.}},
author = {Licheng Xi and Xue Liu and Chaojie Yu and Tao Wang and Junyu Liao and Yanghua Lv and Mian Zhang and Yajie Zhang and Tingting Hu and Ruizheng Liang and Chong Shen},
journal = {Bioactive materials},
year = {2026},
month = oct,
doi = {10.1016/j.bioactmat.2026.10.010},
url = {https://europepmc.org/article/MED/42910182},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Oxygen-vacancy-rich LDH sonosensitizers potentiate narrow-spectrum antibiotics via membrane-disruption strategy for mixed bacterial wound infections.
AU - Licheng Xi
AU - Xue Liu
AU - Chaojie Yu
AU - Tao Wang
AU - Junyu Liao
AU - Yanghua Lv
AU - Mian Zhang
AU - Yajie Zhang
AU - Tingting Hu
AU - Ruizheng Liang
AU - Chong Shen
PY - 2026
DA - 2026/10/14
JO - Bioactive materials
DO - 10.1016/j.bioactmat.2026.10.010
UR - https://europepmc.org/article/MED/42910182
AB - Mixed bacterial infections, including Gram-positive and Gram-negative pathogens, remain a major global health concern. Achieving efficient treatment of synergistic polymicrobial infections stills a tremendous clinical challenge due to antibiotic permeability barriers and resistance. Here, we construct a defect-engineered layered double hydroxide (LDH)-based sonosensitizer platform loaded with clindamycin (a-CoW/CLD) for mixed bacterial infection therapy, which not only demonstrates high efficacy against Gram-positive bacteria, but also exploits reactive oxygen species (ROS)-mediated membrane disruption of Gram-negative bacteria to facilitate CLD penetration, thereby achieving broad-spectrum and highly efficient killing of mixed bacteria. The amorphous a-CoW nanosheets, enriched with oxygen vacancies via acid etching, exhibit a substantially narrowed bandgap (1.22 eV) and markedly enhanced charge separation, producing 22.1-fold higher singlet oxygen under ultrasound (US) irradiation compared with pristine CoW. This ROS burst synergized with CLD achieves potent killing of Staphylococcus aureus (>99.9% at 20 μg mL⁻¹). More critically, ROS disrupt the outer membrane of Gram-negative Escherichia coli, promoting CLD internalization and consequently boosting its lethality by 18.4-fold (from ∼5% to >92.1%). Mechanistic transcriptomics reveals ROS and CLD synergy: ROS disrupt the bacterial membrane via lipid peroxidation, enabling CLD penetration to block protein synthesis and metabolism, while ROS also induce oxidative stress, collectively leading to bacterial death. In a murine wound model co-infected with both pathogens, a-CoW/CLD plus US eradicates >99.9% of mixed bacteria, suppresses systemic inflammation, and significantly accelerates angiogenesis and re-epithelialization. This paradigm establishes a low-dose, broad-spectrum sonodynamic-antibiotic strategy that overcomes antibiotic permeability bottleneck, offering a promising therapeutic avenue against mixed bacterial infections.
SN - 2452-199X
ER -