Endocytic delivery of vancomycin mediated by a synthetic cell surface receptor: Rescue of bacterially infected mammalian cells and tissue targeting in vivo

Siwarutt Boonyarattanakalin, Jianfang Hu, Sheryl A. Dykstra-Rummel, Avery August, Blake R. Peterson

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Extracellular domains of internalizing cell surface receptors are often targeted to enable drug delivery through the mechanism of receptor-mediated endocytosis. To circumvent natural receptors required for endocytic drug delivery, we constructed a small artificial cell surface receptor comprising the membrane anchor N-alkyl-3β-cholesterylamine linked to a d-Phe-d-Ala motif that binds the glycopeptide antibiotic vancomycin. By mimicking membrane association and trafficking properties of cholesterol, this cholesterol-derived synthetic receptor functions as a prosthetic molecule, inserting into plasma membranes of mammalian cells, and rapidly cycling between the cell surface and intracellular endosomes. Human HeLa cells treated with this receptor gained the ability to internalize vancomycin by endocytosis, enabling this cell-impermeable antibiotic to eradicate the lethal intracellular pathogen Listeria monocytogenes and preserving the viability of the host cells in vitro. Moreover, when combined with the synthetic receptor, vancomycin penetrated the blood-brain barrier, accumulating in the brain and other tissues of mice in vivo. Because of their ability to define new pathways across biological membrane barriers, small synthetic cell surface receptors represent promising tools for drug delivery.

Original languageEnglish (US)
Pages (from-to)268-269
Number of pages2
JournalJournal of the American Chemical Society
Volume129
Issue number2
DOIs
StatePublished - Jan 17 2007

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint

Dive into the research topics of 'Endocytic delivery of vancomycin mediated by a synthetic cell surface receptor: Rescue of bacterially infected mammalian cells and tissue targeting in vivo'. Together they form a unique fingerprint.

Cite this