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.

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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