title: Folate receptor-mediated liposomal delivery of a lipophilic boron agent to tumor cells in vitro for neutron capture therapy.
abstract: OBJECTIVE
  This study was aimed at the in vitro evaluations of folate receptor (FR)-targeted liposomes as carriers for a lipophilic boron agent, K[nido-7-CH3(CH2)15-7,8-C2B9H11, in FR-overexpressing tumor cells for neutron capture therapy.
  
  
  METHODS
  Large unilamellar vesicles (-200 nm in diameter) were prepared with the composition of egg PC/chol/K[nido-7-CH3(CH2)15-7,8-C2B9H11] (2:2:1, mol/mol), with an additional 0.5 mol % of folate-PEG-DSPE or PEG-DSPE added for the FR-targeted or nontargeted liposomal formulations, respectively.
  
  
  RESULTS
  Boron-containing, FR-targeted liposomes readily bound to KB cells, an FR-overexpressing cell line, and were internalized via FR-mediated endocytosis. The boron uptake in cells treated with these liposomes was approximately 10 times greater compared with those treated with control liposomes. In contrast, FR-targeted and nontargeted liposomes showed no difference in boron delivery efficiency in F98 cells, which do not express the FR. The subcellular distribution of the boron compound in KB cells treated with the FR-targeted liposomes was investigated by cellular fractionation experiments, which showed that most of the boron compound was found in either the cytosol/endosomal or cell membrane fractions, indicating efficient internalization of the liposomal boron.
  
  
  CONCLUSIONS
  FR-targeted liposomes incorporating the lipophilic boron agent, K[nido-7-CH3(CH2)15-7,8-C2B9H11], into its bilayer were capable of specific receptor binding and receptor-mediated endocytosis in cultured KB cells. Such liposomes warrant further investigations for use in neutron capture therapy.
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus 43210, USA.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Sudimack
authors.forename: Dianne
authors.initials: D
authors.lastname: Adams
authors.forename: Joan
authors.initials: J
authors.lastname: Rotaru
authors.forename: Supriya
authors.initials: S
authors.lastname: Shukla
authors.forename: Junhua
authors.initials: J
authors.lastname: Yan
authors.forename: Masaru
authors.initials: M
authors.lastname: Sekido
authors.forename: Rolf F
authors.initials: RF
authors.lastname: Barth
authors.forename: Werner
authors.initials: W
authors.lastname: Tjarks
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D001896:Boron Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002352:Carrier Proteins / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D058973:Folate Receptors, GPI-Anchored; D006801:Humans; D007624:KB Cells; D008081:Liposomes; D017247:Neutron Capture Therapy / Q000379:methods*; D011956:Receptors, Cell Surface
chemical_list: D001896:Boron Compounds; D002352:Carrier Proteins; D058973:Folate Receptors, GPI-Anchored; D008081:Liposomes; D011956:Receptors, Cell Surface