Erythrocyte membrane-coated nanogel for combinatorial antivirulence and responsive antimicrobial delivery against Staphylococcus aureus infection

J Control Release. 2017 Oct 10:263:185-191. doi: 10.1016/j.jconrel.2017.01.016. Epub 2017 Jan 10.

Abstract

We reported an erythrocyte membrane-coated nanogel (RBC-nanogel) system with combinatorial antivirulence and responsive antibiotic delivery for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. RBC membrane was coated onto the nanogel via a membrane vesicle templated in situ gelation process, whereas the redox-responsiveness was achieved by using a disulfide bond-based crosslinker. We demonstrated that the RBC-nanogels effectively neutralized MRSA-associated toxins in extracellular environment and the toxin neutralization in turn promoted bacterial uptake by macrophages. In intracellular reducing environment, the RBC-nanogels showed an accelerated drug release profile, which resulted in more effective bacterial inhibition. When added to the macrophages infected with intracellular MRSA bacteria, the RBC-nanogels significantly inhibited bacterial growth compared to free antibiotics and non-responsive nanogel counterparts. These results indicate the great potential of the RBC-nanogel system as a new and effective antimicrobial agent against MRSA infection.

Keywords: Antibiotic delivery; Cell membrane coating; Detoxification; Nanomedicine; Staph infection.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / therapeutic use
  • Bacterial Toxins / chemistry
  • Drug Liberation
  • Erythrocyte Membrane*
  • Gels
  • Hemolysin Proteins / chemistry
  • Macrophages / microbiology
  • Male
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Mice, Inbred ICR
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Nanoparticles / therapeutic use
  • Staphylococcal Infections / drug therapy*
  • Vancomycin / administration & dosage*
  • Vancomycin / chemistry
  • Vancomycin / therapeutic use

Substances

  • Anti-Bacterial Agents
  • Bacterial Toxins
  • Gels
  • Hemolysin Proteins
  • staphylococcal alpha-toxin
  • Vancomycin