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

AI Article Synopsis

Article 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 -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 , and preserving the viability of the host cells . Moreover, when combined with the synthetic receptor, vancomycin penetrated the blood brain barrier, accumulating in the brain and other tissues of mice . Because of their ability to define new pathways across biological membrane barriers, small synthetic cell surface receptors represent promising tools for drug delivery.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2536652PMC
http://dx.doi.org/10.1021/ja067674fDOI Listing

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