Open AccessDrug Delivery via Cell Membrane Fusion Using Lipopeptide Modified Liposomes
Author(s) -
Jian Yang,
Azadeh Bahreman,
Geert A. Daudey,
Jeroen Bussmann,
René C. L. Olsthoorn,
Alexander Kros
Publication year - 2016
Publication title -
acs central science
Language(s) - English
Resource type - Journals
eISSN - 2374-7951
pISSN - 2374-7943
DOI - 10.1021/acscentsci.6b00172
Subject(s) - liposome , lipid bilayer fusion , endocytosis , drug delivery , endosome , in vivo , lipopeptide , electroporation , lipid bilayer , in vitro , chemistry , biophysics , ex vivo , membrane , microbiology and biotechnology , cell , biochemistry , biology , genetics , bacteria , organic chemistry , gene
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 cells in vitro and in vivo utilizing 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 many in vitro , ex vivo , and in vivo applications.