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

• Published in: Nature communications Vol. 10; no. 1; pp. 4336 - 12
• Main Authors: Qing, Guangchao, Zhao, Xianxian, Gong, Ningqiang, Chen, Jing, Li, Xianlei, Gan, Yaling, Wang, Yongchao, Zhang, Zhen, Zhang, Yuxuan, Guo, Weisheng, Luo, Yang, Liang, Xing-Jie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.09.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 140/125; 147/135; 147/137; 631/326/22/1434; 631/61/350/2093; 631/61/54/152; 64/60; 692/699/255/1318; Animals; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - pharmacology; Antiinfectives and antibacterials; Bacteria; Bacterial diseases; Bacterial Infections - therapy; Biosafety; Biosynthesis; Cell walls; Drug Delivery Systems; Drug resistance; Drug Resistance, Multiple, Bacterial - drug effects; Fluorescence; Humanities and Social Sciences; I.R. radiation; Imipenem; Imipenem - administration & dosage; Imipenem - pharmacology; Irradiation; Methicillin; Methicillin-Resistant Staphylococcus aureus - drug effects; Mice; Microbial Sensitivity Tests; multidisciplinary; Multidrug resistance; Multidrug resistant organisms; Nanostructures - chemistry; Phase transitions; Phototherapy - adverse effects; Phototherapy - methods; Proof of Concept Study; Science; Science (multidisciplinary); Staphylococcal Skin Infections - therapy; Staphylococcus infections
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12313-3

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. Antibiotic resistance is a major global health challenge. Here, the authors report on a thermoresponsive delivery system for combined photothermal and antibiotic delivery with fluorescent tracking abilities and demonstrate application against antibiotic resistant bacteria in vitro and in vivo.