Biofilm heterogeneity-adaptive photoredox catalysis enables red light-triggered nitric oxide release for combating drug-resistant infections

Jian Cheng, Guihai Gan, Shaoqiu Zheng, Guoying Zhang, Chen Zhu (), Shiyong Liu () and Jinming Hu ()
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Jian Cheng: University of Science and Technology of China
Guihai Gan: University of Science and Technology of China
Shaoqiu Zheng: University of Science and Technology of China
Guoying Zhang: University of Science and Technology of China
Chen Zhu: University of Science and Technology of China
Shiyong Liu: University of Science and Technology of China
Jinming Hu: University of Science and Technology of China

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract The formation of biofilms is closely associated with persistent and chronic infections, and physiological heterogeneity such as pH and oxygen gradients renders biofilms highly resistant to conventional antibiotics. To date, effectively treating biofilm infections remains a significant challenge. Herein, we report the fabrication of micellar nanoparticles adapted to heterogeneous biofilm microenvironments, enabling nitric oxide (NO) release through two distinct photoredox catalysis mechanisms. The key design feature involves the use of tertiary amine (TA) moieties, which function as sacrificial agents to avoid the quenching of photocatalysts under normoxic and neutral pH conditions and proton acceptors at acidic pH to allow deep biofilm penetration. This biofilm-adaptive NO-releasing platform shows excellent antibiofilm activity against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms both in vitro and in a mouse skin infection model, providing a strategy for combating biofilm heterogeneity and biofilm-related infections.

Date: 2023
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DOI: 10.1038/s41467-023-43415-8

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