title: Selective disruption of early/recycling endosomes: release of disulfide-linked cargo mediated by a N-alkyl-3beta-cholesterylamine-capped peptide.
abstract: The use of endocytic uptake pathways to deliver poorly permeable molecules into mammalian cells is often plagued by entrapment and degradation of material in late endosomes and lysosomes. As a strategy to prevent the exposure of cargo to these highly hydrolytic membrane-sealed compartments, we synthesized derivatives of the membrane anchor N-alkyl-3beta-cholesterylamine that selectively target linked compounds to less hydrolytic early/recycling endosomes. By targeting a pH-dependent membrane-lytic dodecapeptide and a disulfide-linked fluorophore to these compartments in Chinese hamster ovary cells or Jurkat lymphocytes, membranes of early/recycling endosomes were selectively disrupted, resulting in cleavage of the disulfide and escape of the fluorophore into the cytosol and nucleus with low toxicity. The ability of appropriately designed N-alkyl-3beta-cholesterylamines to deliver cargo into and release disulfide-linked cargo from relatively nonhydrolytic early/recycling endosomes may be useful for the delivery of a variety of sensitive molecules into living mammalian cells.
authors.affiliation: Integrative Biosciences and Chemistry Graduate Programs, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Sutang
authors.initials: S
authors.lastname: Cai
authors.forename: Blake R
authors.initials: BR
authors.lastname: Peterson
mesh_terms: D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006224:Cricetinae; D003412:Cricetulus; D004220:Disulfides / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D011992:Endosomes / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019169:Jurkat Cells; D010455:Peptides / Q000493:pharmacokinetics*
chemical_list: D004220:Disulfides; D010455:Peptides; C072855:cholesterylamine; D002784:Cholesterol