Issue 38, 2022

A biofilm microenvironment-responsive one-for-all bactericidal nanoplatform for photothermal-augmented multimodal synergistic therapy of pathogenic bacterial biofilm infection

Abstract

Multimodal synergistic bactericidal agents display great potential for fighting biofilm infections. However, the rational design of biofilm microenvironment (BME)-activatable therapeutic agents with excellent specificities, effective eradications and minimal side effects remains a great challenge. Herein, we show a BME-responsive one-for-all bactericidal nanoplatform consisting of Fe3+-doped polydopamine (Fe/PDA)-capped ZnO nanoparticles with a successive assembly of methylene blue (MB) and poly(ethylene glycol) (PEG). In an acidic BME (pH 5.5), the constructed nanoagent (ZnPMp) can realize the co-delivery of dual metal ions (Zn2+ and Fe3+) and MB, and the latter shows an activated photodynamic antibacterial activity when irradiated with 635 nm laser. Zn2+ produced from acid-sensitive dissolution of ZnO is an effective chemical antibacterial agent. Additionally, the released Fe3+ is reduced to Fe2+ by glutathione (GSH) overexpressed in the BME to generate Fe2+/Fe3+ redox couples, which exhibit Fenton catalytic activity to convert endogenous H2O2 to hydroxyl radicals (˙OH) for chemodynamic sterilization and GSH depletion ability to improve ˙OH-induced oxidative damage. Interestingly, the hyperthermia caused by the Fe/PDA layer assisted with 808 nm laser can damage directly bacterial cells, accelerate the release of Zn2+, Fe3+and MB, and promote the catalytic activity of Fe2+/Fe3+ redox couples for photothermal-augmented multimodal antibiofilm therapy. With the help of dual lasers, ZnPMp displays the broad-spectrum antibacterial effect, inhibits effectively the formation of biofilms, and more importantly eliminates bacteria deep in mature biofilms. In addition, ZnPMp can be used to treat biofilm-related infections in vivo with excellent therapeutic performance and minimal toxicity. Overall, the developed ZnPMp may serve as a potential nano-antibacterial agent for intensive anti-infective therapy.

Graphical abstract: A biofilm microenvironment-responsive one-for-all bactericidal nanoplatform for photothermal-augmented multimodal synergistic therapy of pathogenic bacterial biofilm infection

Supplementary files

Article information

Article type
Paper
Submitted
09 jun. 2022
Accepted
17 ago. 2022
First published
18 ago. 2022

J. Mater. Chem. B, 2022,10, 7744-7759

A biofilm microenvironment-responsive one-for-all bactericidal nanoplatform for photothermal-augmented multimodal synergistic therapy of pathogenic bacterial biofilm infection

K. Yang, L. Hai, Z. Wang, H. Li, W. Yi, Y. Luo, J. Li, L. Deng and D. He, J. Mater. Chem. B, 2022, 10, 7744 DOI: 10.1039/D2TB01200F

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