Journal
SCIENCE ADVANCES
Volume 8, Issue 14, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abn1701
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Funding
- National Natural Science Foundation of China [82102586, 81871788, 81802181]
- China Postdoctoral Science Foundation [2020 M671893]
- Fundamental Research Funds for the Central Universities [WK9110000155]
- Natural Science Foundation of Anhui Province, Distinguishing Youth Project [2108085 J41]
- Key Research and Development Projects of Anhui Province [202004j07020013]
- Anhui Provincial Postdoctoral Science Foundation [2019B302]
- Scientific Research Fund of Anhui Education [2020jyxm2316]
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There is a growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. This study proposes a gas-sensitized hyperthermia strategy using a metal-organic framework (MOF)-sealed Prussian blue-based nanocarrier for efficient elimination of biofilms through H2S-induced thermal eradiation.
There is an increasingly growing demand for nonantibiotic strategies to overcome drug resistance in bacterial biofilm infections. Here, a novel gas-sensitized hyperthermia strategy is proposed for appreciable bacteria killing by the smart design of a metal-organic framework (MOF)-sealed Prussian blue-based nanocarrier (MSDG). Once the biofilm microenvironment (BME) is reached, the acidity-activated MOF degradation allows the release of diallyl trisulfide and subsequent glutathione-responsive generation of hydrogen sulfide (H2S) gas. Upon near-infrared irradiation, H2S-sensitized hyperthermia arising from MSDG can efficiently eliminate biofilms through H2S-induced extracellular DNA damage and heat-induced bacterial death. The generated H2S in the biofilm can stimulate the polarization of macrophages toward M-2 phenotype for reshaping immune microenvironment. Subsequently, the secretion of abundant regeneration-related cytokines from M-2 macrophages accelerates tissue regeneration by reversing the infection-induced pro-inflammatory environment in an implant-related infection model. Collectively, such BME-responsive nano-antibacterials can achieve biofilm-specific H2S-sensitized thermal eradiation and immunomodulatory tissue remodeling, thus realizing the renaissance of precision treatment of refractory implantrelated infections.
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