Surface-Adaptive and Initiator-Loaded Graphene as a Light-Induced Generator with Free Radicals for Drug-Resistant Bacteria Eradication

ACS Appl Mater Interfaces. 2019 Jan 16;11(2):1766-1781. doi: 10.1021/acsami.8b12873. Epub 2018 Dec 17.

Abstract

Since generating toxic reactive oxygen species is largely dependent on oxygen, bacteria-infected wounds' hypoxia significantly inhibits photodynamic therapy's antibacterial efficiency. Therefore, a novel therapeutic method for eradicating multidrug-resistant bacteria is developed based on the light-activated alkyl free-radical generation (that is oxygen independent). According to the polydopamine-coated carboxyl graphene (PDA@CG), an initiator-loaded and pH-sensitive heat-producible hybrid of bactericides was synthesized. According to fluorescence/thermal imaging, under the low pH of the bacterial infection sites, this platform turned positively charged, which allows their accumulation in local infection site. The plasmonic heating effects of PDA@CG can make the initiator decomposed to generate alkyl radical (R) under the followed near-infrared light irradiation. As a result, oxidative stress can be elevated, DNA damages in bacteria can be caused, and finally even multidrug-resistance death can be caused under different oxygen tensions. Moreover, our bactericidal could promote wound healing in vivo and negligible toxicity in vivo and in vitro and eliminate abscess. Accordingly, this study proves that combination of oxygen-independent free-radical-based therapy along with a stimulus-responsiveness moiety not only can be used as an effective treatment of multidrug-resistant bacteria infection, but also creates a use of a variety of free radicals for treatment of multidrug-resistant bacteria infection wounds.

Keywords: drug-resistant bacteria; free radicals; graphene; hypoxia; pH responsive.

MeSH terms

  • 3T3 Cells
  • Animals
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Graphite / chemistry
  • Graphite / pharmacology
  • Humans
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Light*
  • Methicillin-Resistant Staphylococcus aureus / growth & development*
  • Mice
  • Mice, Inbred BALB C
  • Photochemotherapy*
  • Polymers* / chemistry
  • Polymers* / pharmacology
  • Reactive Oxygen Species / chemistry*
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / metabolism
  • Staphylococcal Infections / pathology

Substances

  • Anti-Bacterial Agents
  • Indoles
  • Polymers
  • Reactive Oxygen Species
  • polydopamine
  • Graphite