Hybrid Biomimetic Membrane Coated Particles-Mediated Bacterial Ferroptosis for Acute MRSA Pneumonia

Huiqun Hu; Shi Yuan Hua; Xiuhui Lin; Feng Lu; Wenting Zhang; Lihui Zhou; Jiarong Cui; Ruoxi Wang; Jingyan Xia; Feng Xu; Xiaoyuan Chen; Min Zhou

doi:10.1021/acsnano.3c02365

Hybrid Biomimetic Membrane Coated Particles-Mediated Bacterial Ferroptosis for Acute MRSA Pneumonia

ACS Nano. 2023 Jun 27;17(12):11692-11712. doi: 10.1021/acsnano.3c02365. Epub 2023 Jun 13.

Authors

Huiqun Hu¹, Shi Yuan Hua^{2

3}, Xiuhui Lin¹, Feng Lu⁴, Wenting Zhang¹, Lihui Zhou³, Jiarong Cui³, Ruoxi Wang³, Jingyan Xia⁵, Feng Xu^{1

6}, Xiaoyuan Chen^{7

8

9}, Min Zhou^{1

2

3

6}

Affiliations

¹ Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
² Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Haining 314400, China.
³ Institute of Translational Medicine, Zhejiang University, Hangzhou 310029, China.
⁴ Orthopaedic Department, Taizhou Central Hospital, Affiliate Hospital of Taizhou University, Taizhou, Zhejiang Province 318000, China.
⁵ Department of Radiation Therapy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
⁶ Research Center for Life Science and Human Health, Binjiang Institute of Zhejiang University, Hangzhou 310053, China.
⁷ Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and Faculty of Engineering, National University of Singapore, Singapore 119074, Singapore.
⁸ Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, Singapore.
⁹ Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore.

PMID: 37310363
DOI: 10.1021/acsnano.3c02365

Abstract

Acute methicillin resistant Staphylococcus aureus (MRSA) pneumonia is one of the most frequently seen lung infection diseases with high morbidity and mortality. It is urgent to explore an efficient antibacterial strategy owing to the increase of drug resistance, virulence, and pathogenicity of MRSA. It was found that Fe₃O₄ can induce ferroptosis in MRSA, but its effect was inhibited by glutathione (GSH) to a certain extent, while cinnamaldehyde (CA) can enhance ferroptosis by consuming GSH. As a bacterial quorum sensing (QS) inhibitor, CA can suppress the QS system and further exert its antibacterial and antibiofilm effects. Here, we developed an Fe₃O₄-based ferroptosis inducer to promote ferroptosis in MRSA, interrupt the QS, destroy biofilm, and thus effectively treat acute MRSA pneumonia. We used sodium alginate (SA) to wrap Fe₃O₄ and CA to form particles, and then coated the surface with a hybrid biomimetic membrane composed of an erythrocyte membrane and platelet membrane to obtain lung targeted antibacterial particles (mFe-CA). Under ultrasonic (US) stimulation, mFe-CA can efficiently release Fe₃O₄ and CA, thereby synergically inducing MRSA death with the characteristics of ferroptosis, including mass ROS production, lipid peroxidation, GSH depletion, and respiratory chain suppression. Furthermore, mFe-CA + US can inhibit the QS system, remove biofilms, and reduce strain virulence. In the mouse model of MRSA pneumonia, mFe-CA + US treatment markedly advanced the survival rate of the mice, reduced the bacterial load in the lungs, and alleviated the inflammatory damage, but there was no obvious toxicity. This study proposes an antibacterial substitute to induce ferroptosis of MRSA, which may provide a foreground for overcoming microbial drug resistance and fighting biofilm-associated infections and also provides a target and theoretical basis for clinical treatment of acute MRSA pneumonia.

Keywords: cinnamaldehyde; ferroptosis; hybrid biomimetic membrane; methicillin resistant Staphylococcus aureus; pneumonia; quorum sensing.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anti-Bacterial Agents / pharmacology
Biofilms
Biomimetics
Ferroptosis*
Methicillin-Resistant Staphylococcus aureus*
Mice
Microbial Sensitivity Tests
Pneumonia*

Substances

Anti-Bacterial Agents