Coating of a Novel Antimicrobial Nanoparticle with a Macrophage Membrane for the Selective Entry into Infected Macrophages and Killing of Intracellular Staphylococci

Yuanfeng Li, Yong Liu, Yijin Ren, Linzhu Su, Ang Li, Yingli An, Vincent Rotello, Zhanzhan Zhang, Yin Wang, Yang Liu, Sidi Liu, Jian Liu, Jon D. Laman, Linqi Shi, Henny C. van der Mei*, Henk J. Busscher

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

Internalization ofStaphylococcus aureusby macrophages can inactivate bacterial killing mechanisms, allowing intracellular residence and dissemination of infection. Concurrently, these staphylococci can evade antibiotics that are frequently unable to pass mammalian cell membranes. A binary, amphiphilic conjugate composed of triclosan and ciprofloxacin is synthesized that self-assemble through micelle formation into antimicrobial nanoparticles (ANPs). These novel ANPs are stabilized through encapsulation in macrophage membranes, providing membrane-encapsulated, antimicrobial-conjugated NPs (Me-ANPs) with similar protein activity, Toll-like receptor expression and negative surface charge as their precursor murine macrophage/human monocyte cell lines. The combination of Toll-like receptors and negative surface charge allows uptake of Me-ANPs by infected macrophages/monocytes through positively charged, lysozyme-rich membrane scars created during staphylococcal engulfment. Me-ANPs are not engulfed by more negatively charged sterile cells possessing less lysozyme at their surface. The Me-ANPs kill staphylococci internalized in macrophages in vitro. Me-ANPs likewise kill staphylococci more effectively than ANPs without membrane-encapsulation or clinically used ciprofloxacin in a mouse peritoneal infection model. Similarly, organ infections in mice created by dissemination of infected macrophages through circulation in the blood are better eradicated by Me-ANPs than by ciprofloxacin. These unique antimicrobial properties of macrophage-monocyte Me-ANPs provide a promising direction for human clinical application to combat persistent infections.

Original languageEnglish
Article number2004942
Number of pages16
JournalAdvanced Functional Materials
Issue number48
DOIs
Publication statusPublished - 16-Sep-2020

Keywords

  • bacterial infections
  • cell membrane encapsulation
  • ciprofloxacin
  • Toll-like receptors
  • triclosan
  • TRANSBILAYER DISTRIBUTION
  • PERITONEAL-MACROPHAGES
  • DOUBLE-BLIND
  • AUREUS
  • INNATE
  • TRICLOSAN
  • THERAPY
  • CELLS
  • PHOSPHOLIPIDS
  • NANOCARRIERS

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