Hybrid Biomimetic Membrane Coated Particles-Mediated Bacterial Ferroptosis for Acute MRSA Pneumonia.
Huiqun HuShi Yuan HuaXiuhui LinFeng LuWenting ZhangLihui ZhouJiarong CuiRuoxi WangJingyan XiaFeng XuXiaoyuan Shawn ChenMin ZhouPublished in: ACS nano (2023)
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 Fe 3 O 4 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 Fe 3 O 4 -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 Fe 3 O 4 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 Fe 3 O 4 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.
Keyphrases
- methicillin resistant staphylococcus aureus
- staphylococcus aureus
- cell death
- respiratory failure
- biofilm formation
- liver failure
- pseudomonas aeruginosa
- mouse model
- escherichia coli
- drug induced
- dna damage
- extracorporeal membrane oxygenation
- silver nanoparticles
- antimicrobial resistance
- combination therapy
- skeletal muscle
- microbial community
- wound healing
- metabolic syndrome
- hepatitis b virus
- fatty acid
- essential oil
- drug delivery
- fluorescent probe
- acute respiratory distress syndrome
- free survival