title: Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate.
abstract: Poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles with anionic surface charge were surface coated with cationic di-block copolymer, poly(L-lysine)-poly(ethylene glycol)-folate (PLL-PEG-FOL) conjugate, for enhancing their site-specific intracellular delivery against folate receptor overexpressing cancer cells. The PLGA nanoparticles coated with the conjugate were characterized in terms of size, surface charge, and change in surface composition by XPS. By employing the flow cytometry method and confocal image analysis, the extent of cellular uptake was comparatively evaluated under various conditions. PLL-PEG-FOL coated PLGA nanoparticles demonstrated far greater extent of cellular uptake to KB cells, suggesting that they were mainly taken up by folate receptor-mediated endocytosis. The enhanced cellular uptake was also observed even in the presence of serum proteins, possibly due to the densely seeded PEG chains. The PLL-PEG-FOL coated PLGA nanoparticles could be potentially applied for cancer cell targeted delivery of various therapeutic agents.
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, South Korea.
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jeong
authors.forename: Ki Woo
authors.initials: KW
authors.lastname: Chun
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
mesh_terms: D002352:Carrier Proteins / Q000187:drug effects; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D058973:Folate Receptors, GPI-Anchored; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D006016:Glycolates / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D019344:Lactic Acid; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine / Q000737:chemistry / Q000493:pharmacokinetics*; D011956:Receptors, Cell Surface / Q000187:drug effects; D012680:Sensitivity and Specificity; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014965:X-Rays
chemical_list: D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D006016:Glycolates; D011956:Receptors, Cell Surface; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011107:Polylysine; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D005492:Folic Acid