Silver-Containing Titanium Dioxide Nanocapsules for Combating Multidrug-Resistant Bacteria

Int J Nanomedicine. 2020 Feb 25:15:1267-1281. doi: 10.2147/IJN.S231949. eCollection 2020.

Abstract

Background: Joint arthroplasty has improved the quality of life of patients worldwide, but infections of the prosthesis are frequent and cause significant morbidity. Antimicrobial coatings for implants promise to prevent these infections.

Methods: We have synthesized nanocapsules of titanium dioxide in amorphous or anatase form containing silver as antibacterial agent and tested their impact on bacterial growth. Furthermore, we explored the possible effect of the nanocapsules on the immune system. First, we studied their uptake into macrophages using a combination of electron microscopy and energy-dispersive spectroscopy. Second, we exposed immune cells to the nanocapsules and checked their activation state by flow cytometry and enzyme-linked immunosorbent assay.

Results: Silver-containing titanium dioxide nanocapsules show strong antimicrobial activity against both E. coli and S. aureus and even against a multidrug-resistant strain of S. aureus. We could demonstrate the presence of the nanocapsules in macrophages, but, importantly, the nanocapsules did not affect cell viability and did not activate proinflammatory responses at doses up to 20 μg/mL.

Conclusion: Our bactericidal silver-containing titanium dioxide nanocapsules fulfill important prerequisites for biomedical use and represent a promising material for the coating of artificial implants.

Keywords: antimicrobial effect; immune cell uptake; multidrug-resistant S. aureus; silver nanoparticles; titanium dioxide nanocapsules.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Coated Materials, Biocompatible / chemistry
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Escherichia coli / drug effects
  • Macrophages / drug effects
  • Mice, Inbred C57BL
  • Microbial Sensitivity Tests
  • Nanocapsules / chemistry*
  • Nanocapsules / therapeutic use
  • Silver / chemistry
  • Silver / pharmacokinetics
  • Staphylococcus aureus / drug effects
  • Titanium / chemistry

Substances

  • Anti-Bacterial Agents
  • Coated Materials, Biocompatible
  • Nanocapsules
  • titanium dioxide
  • Silver
  • Titanium

Grants and funding

This research was financially supported by the Swiss Competence Center in Energy Research (SCCER) for Heat and Electricity Storage, the National Competence Center in Research (NCCR) Bio-Inspired Materials (Grant Number 51NF40_141849), the Swiss National Science Foundation (grant numbers 156372 and 156871), and the Commission for Technology and Innovation (CTI). We are also grateful to the University of Fribourg, the Adolphe Merkle Foundation and the FriMat for their support.