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Published on: September 27, 2024
Biomineralized nanozymes remodel the infectious microenvironment for precision MRSA pneumonia therapy
Hening Liu1, Yue Yin1, Ziwei Yan1
1State Key Laboratory of Natural Medicines, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, PR China; NMPA Key Laboratory for Research and Evaluation of Cosmetics, China Pharmaceutical University, Nanjing 211198, PR China; Wuxi Research Center for Innovative Medicines and Life Health, Wuxi Innovation Research Institute of China Pharmaceutical University, Wuxi 214112, PR China.
Abstract:
Methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia remains clinically challenging because antibiotic monotherapy is often insufficient to eradicate bacteria at pulmonary lesions and fails to resolve infection-amplified oxidative and inflammatory injury. Herein, we report a neutrophil membrane-cloaked, melanin-biomineralized MnO2 nanozyme platform co-loaded with curcumin and vancomycin (VC@NMM) for targeted antibacterial and immunoregulatory therapy of MRSA pneumonia. Through melanin-mediated biomineralization with KMnO4, a biocompatible MnO2 nanozyme framework is constructed with abundant interfacial sites for dual-drug loading and catalytic microenvironment regulation. In this integrated system, vancomycin directly inhibits MRSA growth, curcumin potentiates antibacterial activity and attenuates oxidative inflammation, and the MnO2 nanozyme mediates ROS scavenging, H2O2 decomposition, oxygenation improvement, and bacterial disruption. Neutrophil membrane cloaking further confers prolonged circulation and inflammation-tropic accumulation at MRSA-colonized lung tissues. Consequently, VC@NMM effectively reduces the required vancomycin dosage, disrupts bacterial integrity, induces protein leakage, impairs ATP metabolism, and suppresses MRSA survival in vitro. In MRSA pneumonia mouse model, VC@NMM significantly reduces pulmonary bacterial burden, alleviates edema and histopathological injury, inhibits ROS/NF-κB inflammatory signaling, remodels macrophage polarization, and prolongs survival. Collectively, this work establishes a biomineralized biomimetic nanozyme strategy that couples targeted antibiotic delivery with catalytic microenvironment remodeling and inflammation resolution for effective bacterial pneumonia therapy.
Insights
A novel nanozyme platform effectively treats MRSA pneumonia by combining vancomycin and curcumin with manganese dioxide. This biomimetic approach targets bacteria and reduces inflammation for improved therapeutic outcomes.
Area of Science:
- Biomaterials Science
- Nanomedicine
- Infectious Diseases
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia presents treatment challenges due to insufficient bacterial eradication and unresolved inflammation with monotherapy.
- Current therapies struggle to address both the bacterial load and the associated oxidative and inflammatory damage in pulmonary lesions.
Purpose of the Study:
- To develop a neutrophil membrane-cloaked, melanin-biomineralized MnO2 nanozyme platform (VC@NMM) for targeted antibacterial and immunoregulatory therapy of MRSA pneumonia.
- To evaluate the synergistic therapeutic effects of vancomycin, curcumin, and MnO2 nanozyme in a preclinical MRSA pneumonia model.
Main Methods:
- Fabrication of a biocompatible MnO2 nanozyme framework via melanin-mediated biomineralization for dual-drug loading (vancomycin and curcumin).
- Cloaking the nanozyme with neutrophil membranes to enhance circulation time and target lung tissues.
- In vitro assessment of antibacterial activity and in vivo evaluation in a mouse model of MRSA pneumonia, monitoring bacterial burden, inflammation, and survival.
Main Results:
- VC@NMM demonstrated effective in vitro inhibition of MRSA growth, disruption of bacterial integrity, and suppression of survival.
- In vivo studies showed significant reduction in pulmonary bacterial load, alleviation of edema and injury, and suppression of inflammatory signaling (ROS/NF-κB).
- The nanozyme platform promoted macrophage polarization and prolonged survival in the MRSA pneumonia mouse model.
Conclusions:
- The developed biomineralized biomimetic nanozyme strategy offers a promising approach for treating bacterial pneumonia.
- VC@NMM effectively combines targeted antibiotic delivery with catalytic microenvironment remodeling and inflammation resolution.
- This integrated nanozyme platform shows potential for enhanced therapeutic efficacy in challenging infections like MRSA pneumonia.
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