title: Delivery of macromolecules into living cells: a method that exploits folate receptor endocytosis.
abstract: Difficulties with the nondestructive delivery of macromolecules into living cells have limited the potential applications of antibodies, genes, enzymes, peptides, and antisense oligonucleotides in biology and medicine. We have found, however, that the natural endocytosis pathway for the vitamin folate can be exploited to nondestructively introduce macromolecules into cultured cells if the macromolecule is first covalently linked to folate. Thus, treatment of KB cells with folate-conjugated ribonuclease, horseradish peroxidase, serum albumin, IgG, or ferritin allowed delivery of greater than 10(6) copies of the macromolecules within a 2-hr period. Cytochemical staining using 4-chloro-1-naphthol further demonstrated that the horseradish peroxidase retained activity for at least 6 hr after internalization. Since folate is an essential vitamin required in substantial quantities by virtually all cells, these observations may open the possibility of scientific and medical applications for many of the above macromolecules.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, IN 47907.
authors.forename: C P
authors.initials: CP
authors.lastname: Leamon
authors.forename: P S
authors.initials: PS
authors.lastname: Low
mesh_terms: D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line; D004705:Endocytosis; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D006735:Horseradish Peroxidase / Q000737:chemistry; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D011956:Receptors, Cell Surface; D012259:Ribonuclease, Pancreatic / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D007074:Immunoglobulin G; D011506:Proteins; D011956:Receptors, Cell Surface; D012710:Serum Albumin, Bovine; D005492:Folic Acid; D006735:Horseradish Peroxidase; D012259:Ribonuclease, Pancreatic