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

• Published in: Nature communications Vol. 14; no. 1; pp. 7510 - 12
• Main Authors: Cheng, Jian, Gan, Guihai, Zheng, Shaoqiu, Zhang, Guoying, Zhu, Chen, Liu, Shiyong, Hu, Jinming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 18.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 14/34; 14/63; 140/131; 140/58; 147/135; 147/28; 38/91; 639/301/54/990; 639/301/923/1028; 639/638/298/923/1028; Antibiotics; Biofilms; Catalysis; Ciprofloxacin; Drug resistance; Fabrication; Heterogeneity; Humanities and Social Sciences; Infections; Microenvironments; multidisciplinary; Nanoparticles; Nitric oxide; pH effects; Photoredox catalysis; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-43415-8

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. Biofilms are heterogeneous and difficult to treat. Here, the authors report the preparation of micellar nanoparticles specifically for the treatment of biofilm, that release nitric oxide through two distinct photoredox catalysis mechanisms.