title: Drug Delivery via Cell Membrane Fusion Using Lipopeptide Modified Liposomes.
abstract: Efficient delivery of drugs to living cells is still a major challenge. Currently, most methods rely on the endocytotic pathway resulting in low delivery efficiency due to limited endosomal escape and/or degradation in lysosomes. Here, we report a new method for direct drug delivery into the cytosol of live cellsin vitroandinvivoutilizing targeted membrane fusion between liposomes and live cells. A pair of complementary coiled-coil lipopeptides was embedded in the lipid bilayer of liposomes and cell membranes respectively, resulting in targeted membrane fusion with concomitant release of liposome encapsulated cargo including fluorescent dyes and the cytotoxic drug doxorubicin. Using a wide spectrum of endocytosis inhibitors and endosome trackers, we demonstrate that the major site of cargo release is at the plasma membrane. This method thus allows for the quick and efficient delivery of drugs and is expected to have manyinvitro,ex vivo, andinvivoapplications.
authors.affiliation: Department of Supramolecular Chemistry & Biomaterials, Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, Leiden, 2300 RA, The Netherlands.
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Supramolecular Chemistry & Biomaterials, Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, Leiden, 2300 RA, The Netherlands.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Bahreman
authors.affiliation: Department of Supramolecular Chemistry & Biomaterials, Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, Leiden, 2300 RA, The Netherlands.
authors.forename: Geert
authors.initials: G
authors.lastname: Daudey
authors.affiliation: Department of Supramolecular Chemistry & Biomaterials, Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, Leiden, 2300 RA, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Bussmann
authors.affiliation: Department of Supramolecular Chemistry & Biomaterials, Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, Leiden, 2300 RA, The Netherlands.
authors.forename: René C L
authors.initials: RC
authors.lastname: Olsthoorn
authors.affiliation: Department of Supramolecular Chemistry & Biomaterials, Leiden Institute of Chemistry, Leiden University , P.O. Box 9502, Leiden, 2300 RA, The Netherlands.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kros