Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection

Guangchao Qing, Xianxian Zhao, Ningqiang Gong, Jing Chen, Xianlei Li, Yaling Gan, Yongchao Wang, Zhen Zhang, Yuxuan Zhang, Weisheng Guo (), Yang Luo () and Xing-Jie Liang ()
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Guangchao Qing: Chongqing University
Xianxian Zhao: Army Medical University
Ningqiang Gong: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China
Jing Chen: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China
Xianlei Li: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China
Yaling Gan: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China
Yongchao Wang: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China
Zhen Zhang: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China
Yuxuan Zhang: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China
Weisheng Guo: Guangzhou Medical University
Yang Luo: Chongqing University
Xing-Jie Liang: CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China

Nature Communications, 2019, vol. 10, issue 1, 1-12

Abstract: Abstract New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.

Date: 2019
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DOI: 10.1038/s41467-019-12313-3

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