title: Multicomponent folate-targeted magnetoliposomes: design, characterization, and cellular uptake.
abstract: Folate-targeted cationic magnetoliposomes (FTMLs) have been prepared with coencapsulated doxorubicin (DOX) and anionic superparamagnetic iron oxide (SPIO) nanoparticles (NPs) with 5 nm γ-Fe(2)O(3) cores and 16 nm hydrodynamic diameters. NP encapsulation (89%) was confirmed by cryogenic transmission electron microscopy (TEM), and the presence of the oppositely charged NPs did not cause liposome aggregation. The FTMLs had an average diameter of 174 ± 53 nm and existed as unilamellar and cup-shaped liposomes, which was attributed to dissimilar lipid packing parameters and the presence of PEG-lipids. A 3-fold increase in DOX release was achieved over 2 hours when the encapsulated SPIO NPs were heated by an alternating current electromagnetic field operating at radio frequencies (RF). Results with human cervical cancer cells (HeLa), which have been shown to exhibit high folate receptor (FR) expression, confirmed FTML surface binding and cellular uptake. In contrast, no uptake was observed for lower FR-expressing human breast carcinoma cells (ZR-75-1).
  
  
  BACKGROUND
  This study discusses the design and cellular uptake of multifunctional folate-targeted cationic magnetoliposomes enabling doxorubicin delivery and SPIO labeling.
authors.affiliation: Department of Chemical Engineering, University of Rhode Island, Kingston, Rhode Island 02881, USA. bothun@egr.uri.edu
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Bothun
authors.forename: Alline
authors.initials: A
authors.lastname: Lelis
authors.forename: Yanjing
authors.initials: Y
authors.lastname: Chen
authors.forename: Kyle
authors.initials: K
authors.lastname: Scully
authors.forename: Linnea E
authors.initials: LE
authors.lastname: Anderson
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Stoner
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D058185:Magnetite Nanoparticles; D004317:Doxorubicin; D005492:Folic Acid