title: Transfection of folate-polylysine DNA complexes: evidence for lysosomal delivery.
abstract: We are utilizing the folate receptor for the intracellular delivery of DNA. In this study, a folate-poly-L-lysine (FPLL) conjugate was synthesized and equilibrated with plasmid DNA encoding the firefly luciferase gene. The FPLL-DNA complexes were added to KB cells treated with chloroquine. Luciferase activity of cells incubated with FPLL-DNA was 6-fold higher than of cells exposed to poly-L-lysine (PLL)-DNA. The addition of free folic acid competitively inhibited the enhancement of gene expression. Removal of chloroquine from the media significantly inhibited transfection efficiency of FPLL-DNA complexes. We conclude that FPLL-DNA complexes are delivered into KB cells via folate receptor-mediated endocytosis and likely follow a lysosomal pathway into the cytoplasm.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena 91125, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Mislick
authors.forename: J D
authors.initials: JD
authors.lastname: Baldeschwieler
authors.forename: J F
authors.initials: JF
authors.lastname: Kayyem
authors.forename: T J
authors.initials: TJ
authors.lastname: Meade
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D001517:Coleoptera; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics*; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005069:Evaluation Studies as Topic; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000008:administration & dosage* / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008247:Lysosomes / Q000378:metabolism*; D015394:Molecular Structure; D010957:Plasmids / Q000235:genetics; D011107:Polylysine / Q000008:administration & dosage* / Q000737:chemistry; D011956:Receptors, Cell Surface; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D004337:Drug Carriers; D058973:Folate Receptors, GPI-Anchored; D011956:Receptors, Cell Surface; D011107:Polylysine; D004247:DNA; D005492:Folic Acid; D008156:Luciferases