Boron doped silver-copper alloy nanoparticle targeting intracellular S. aureus in bone cells

PLoS One. 2020 Apr 10;15(4):e0231276. doi: 10.1371/journal.pone.0231276. eCollection 2020.

Abstract

Objectives: Alloyed metallic nanoparticles of silver and copper are effective against intracellular infection. However, systemic toxicity may arise due to the non-specific delivery of the nanoparticles. In addressing the issue, this study deals with the targeting of silver-copper-boron (ACB) nanoparticles to infected osteoblasts, which could decrease systemic toxicity and form the basis of targeting specific markers expressed in bone infections.

Methods: ACB nanoparticles were synthesized and conjugated to the Cadherin-11 antibody (OBAb). The effect of targeting nanoparticles against extracellular and intracellular S. aureus was determined by enumeration of bacterial growth. The binding of the targeting nanoparticles to infected osteoblasts as well as the visualization of live/dead bacteria due to treatment was carried out using fluorescence microscopy. MTT assay was used to determine the viability of osteoblasts with different concentrations of the nanoparticles.

Results: The ACB nanoparticles conjugated to OBAb (ACB-OBAb) were effective against extracellular S. aureus. The ACB-OBAb nanoparticles showed a 1.32 log reduction of intracellular S. aureus at a concentration of 1mg/L. The ACB-OBAb nanoparticles were able to bind to the infected osteoblast and showed toxicity to osteoblasts at levels ≥20mg/L. Also, the percentage of silver, copper, and boron in the nanoparticles determined the effectiveness of their antibacterial activity.

Conclusion: The ACB-OBAb nanoparticles were able to target the osteoblasts and demonstrated significant antibacterial activity against intracellular S. aureus. Targeting shows promise as a strategy to target specific markers expressed on infected osteoblasts for efficient nanoparticle delivery, and further animal studies are recommended to test its efficacy in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alloys / pharmacology*
  • Anti-Bacterial Agents / pharmacology
  • Bone and Bones / cytology*
  • Boron / pharmacology*
  • Cadherins / immunology
  • Cell Line
  • Copper / pharmacology*
  • Endocytosis / drug effects
  • Humans
  • Intracellular Space / drug effects
  • Intracellular Space / microbiology*
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / ultrastructure
  • Microbial Sensitivity Tests
  • Osteoblasts / drug effects
  • Osteoblasts / microbiology
  • Silver / pharmacology*
  • Staphylococcus aureus / drug effects*

Substances

  • Alloys
  • Anti-Bacterial Agents
  • Cadherins
  • osteoblast cadherin
  • Silver
  • Copper
  • Boron

Grants and funding

This work was supported by the Qatar National Research fund grant number NPRP8-272-1744-3-357X to YH. In addition, the publication of this paper was funded by the Qatar National Library.