Nanosilver-Decorated Biodegradable Mesoporous Organosilica Nanoparticles for GSH-Responsive Gentamicin Release and Synergistic Treatment of Antibiotic-Resistant Bacteria

Int J Nanomedicine. 2021 Jul 6:16:4631-4642. doi: 10.2147/IJN.S315067. eCollection 2021.

Abstract

Purpose: Antibiotic-resistant bacteria are pathogens that have emerged as a serious public health risk. Thus, there is an urgent need to develop a new generation of anti-bacterial materials to kill antibiotic-resistant bacteria.

Methods: Nanosilver-decorated mesoporous organosilica nanoparticles (Ag-MONs) were fabricated for co-delivery of gentamicin (GEN) and nanosilver. After investigating the glutathione (GSH)-responsive matrix degradation and controlled release of both GEN and silver ions, the anti-bacterial activities of Ag-MONs@GEN were systematically determined against several antibiotic-susceptible and antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Furthermore, the cytotoxic profiles of Ag-MONs@GEN were evaluated.

Results: The GEN-loaded nanoplatform (Ag-MONs@GEN) showed glutathione-responsive matrix degradation, resulting in the simultaneous controlled release of GEN and silver ions. Ag-MONs@GEN exhibited excellent anti-bacterial activities than Ag-MONs and GEN alone via inducing ROS generation, especially enhancing synergetic effects against four antibiotic-resistant bacteria including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis. Moreover, the IC50 values of Ag-MONs@GEN in L929 and HUVECs cells were 313.6 ± 15.9 and 295.7 ± 12.3 μg/mL, respectively, which were much higher than their corresponding minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values.

Conclusion: Our study advanced the development of Ag-MONs@GEN for the synergistic and safe treatment of antibiotic-resistant bacteria.

Keywords: GSH-responsive release; antibiotics-resistant bacteria; gentamicin; mesoporous organosilica nanoparticles; nanosilver.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Drug Liberation
  • Drug Resistance, Microbial / drug effects*
  • Drug Synergism
  • Gentamicins / pharmacology*
  • Glutathione / chemistry*
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Mice
  • Microbial Sensitivity Tests
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Silicon Dioxide / chemistry*
  • Silver / chemistry*

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • colloidal silver
  • Silver
  • Silicon Dioxide
  • Glutathione