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

Receptor-mediated drug delivery is a Trojan horse approach for the release of therapeutics into cells, tissues, or organs. By coupling drugs to ligands of cell surface receptors, ligand-drug conjugates can accumulate in specific tissues and can be internalized by cells through the mechanism of receptor-mediated endocytosis.1 Receptors targeted in this way include the low-density lipoprotein (LDL) receptor,2 transferrin receptors,3 and folate receptors.4 Receptors involved in the passage of nutrients across the blood-brain barrier through the related mechanism of receptor-mediated transcytosis have been similarly targeted to deliver drugs and imaging agents into the brain.5 This latter strategy is of significant interest because less than 2% of all drugs are capable of penetrating the bloodbrain barrier.5 We report here a method for synthetic receptor-mediated drug delivery. This approach was applied to the glycopeptide antibiotic vancomycin (1), a drug of last resort against bacterial pathogens