Reconstructed Apoptotic Bodies as Targeted "nano Decoys" to Treat Intracellular Bacterial Infections within Macrophages and Cancer Cells

Rajendran J.C. Bose, Nagendran Tharmalingam, Fernando J. Garcia Marques, Uday Kumar Sukumar, Arutselvan Natarajan, Yitian Zeng, Elise Robinson, Abel Bermudez, Edwin Chang, Frezghi Habte, Sharon J. Pitteri, Jason R. McCarthy, Sanjiv S. Gambhir, Tarik F. Massoud, Eleftherios Mylonakis, Ramasamy Paulmurugan

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Staphylococcus aureus (S. aureus) is a highly pathogenic facultative anaerobe that in some instances resides as an intracellular bacterium within macrophages and cancer cells. This pathogen can establish secondary infection foci, resulting in recurrent systemic infections that are difficult to treat using systemic antibiotics. Here, we use reconstructed apoptotic bodies (ReApoBds) derived from cancer cells as "nano decoys" to deliver vancomycin intracellularly to kill S. aureus by targeting inherent "eat me" signaling of ApoBds. We prepared ReApoBds from different cancer cells (SKBR3, MDA-MB-231, HepG2, U87-MG, and LN229) and used them for vancomycin delivery. Physicochemical characterization showed ReApoBds size ranges from 80 to 150 nm and vancomycin encapsulation efficiency of 60 ± 2.56%. We demonstrate that the loaded vancomycin was able to kill intracellular S. aureus efficiently in an in vitro model of S. aureus infected RAW-264.7 macrophage cells, and U87-MG (p53-wt) and LN229 (p53-mt) cancer cells, compared to free-vancomycin treatment (P < 0.001). The vancomycin loaded ReApoBds treatment in S. aureus infected macrophages showed a two-log-order higher CFU reduction than the free-vancomycin treatment group. In vivo studies revealed that ReApoBds can specifically target macrophages and cancer cells. Vancomycin loaded ReApoBds have the potential to kill intracellular S. aureus infection in vivo in macrophages and cancer cells.

Original languageEnglish (US)
Pages (from-to)5818-5835
Number of pages18
JournalACS Nano
Volume14
Issue number5
DOIs
StatePublished - May 26 2020

Keywords

  • Staphylococcus aureus
  • antibiotics
  • apoptotic bodies
  • bacterial therapy
  • cancer cells
  • macrophages
  • vancomycin

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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