Folate receptor mediated intracellular protein delivery using PLL-PEG-FOL conjugate.
To develop a receptor-mediated intracellular delivery system that can transport therapeutic proteins or other bioactive macromolecules into a specific cell, a di-block copolymer conjugate, poly(L-lysine)-poly(ethylene glycol)-folate (PLL-PEG-FOL), was synthesized. The PLL-PEG-FOL conjugate was physically complexed with fluorescein isothiocyanate conjugated bovine serum albumin (FITC-BSA) in an aqueous phase by ionic interactions. Cellular uptake of PLL-PEG-FOL/FITC-BSA complexes was greatly enhanced against a folate receptor over-expressing cell line (KB cells) compared to a folate receptor deficient cell line (A549 cells). The presence of an excess amount of free folate (1 mM) in the medium inhibited the intracellular delivery of PLL-PEG-FOL/FITC-BSA complexes. This suggests that the enhanced cellular uptake of FITC-BSA by KB cells in a specific manner was attributed to folate receptor-mediated endocytosis of the complexes having folate moieties on the surface. The PLL-PEG-FOL di-block copolymer could be potentially applied for intracellular delivery of a wide range of other biological active agents that have negative charges on the surface.
Hwa Kim
Sun
S
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
Hoon Jeong
Ji
J
Joe
Cheol O
CO
Gwan Park
Tae
T
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000502:physiology; D005079:Excipients; D016650:Fluorescein-5-isothiocyanate; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid; D006801:Humans; D007624:KB Cells; D018613:Microscopy, Confocal; D008970:Molecular Weight; D011092:Polyethylene Glycols; D011107:Polylysine; D011506:Proteins / Q000008:administration & dosage* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012710:Serum Albumin, Bovine; D013056:Spectrophotometry, Ultraviolet
D002352:Carrier Proteins; D005079:Excipients; D058973:Folate Receptors, GPI-Anchored; D011506:Proteins; D011956:Receptors, Cell Surface; D011107:Polylysine; D012710:Serum Albumin, Bovine; D011092:Polyethylene Glycols; D005492:Folic Acid; D016650:Fluorescein-5-isothiocyanate