title: Liposome-based delivery of a boron-containing cholesteryl ester for high-LET particle-induced damage of prostate cancer cells: a boron neutron capture therapy study.
abstract: OBJECTIVE
  The efficacy of a boron-containing cholesteryl ester compound (BCH) as a boron neutron capture therapy (BNCT) agent for the targeted irradiation of PC-3 human prostate cancer cells was examined.
  
  
  METHODS
  Liposome-based delivery of BCH was quantified with inductively coupled plasma-mass spectrometry (ICP-MS) and high-performance liquid chromatography (HPLC). Cytotoxicity of the BCH-containing liposomes was evaluated with neutral red, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), and lactate dehydrogenase assays. Colony formation assays were utilized to evaluate the decrease in cell survival due to high-linear energy transfer (LET) particles resulting from (10)B thermal neutron capture.
  
  
  RESULTS
  BCH delivery by means of encapsulation in a lipid bilayer resulted in a boron uptake of 35.2 ± 4.3 μg/10(9) cells, with minimal cytotoxic effects. PC-3 cells treated with BCH and exposed to a 9.4 × 10(11) n/cm(2) thermal neutron fluence yielded a 20-25% decrease in clonogenic capacity. The decreased survival is attributed to the generation of high-LET α particles and (7)Li nuclei that deposit energy in densely ionizing radiation tracks.
  
  
  CONCLUSIONS
  Liposome-based delivery of BCH is capable of introducing sufficient boron to PC-3 cells for BNCT. High-LET α particles and (7)Li nuclei generated from (10)B thermal neutron capture significantly decrease colony formation ability in the targeted PC-3 cells.
authors.affiliation: Armed Forces Radiobiology Research Institute , Bethesda, MD.
authors.forename: Ian
authors.initials: I
authors.lastname: Gifford
authors.forename: Wyatt
authors.initials: W
authors.lastname: Vreeland
authors.forename: Slavica
authors.initials: S
authors.lastname: Grdanovska
authors.forename: Eric
authors.initials: E
authors.lastname: Burgett
authors.forename: John
authors.initials: J
authors.lastname: Kalinich
authors.forename: Vernieda
authors.initials: V
authors.lastname: Vergara
authors.forename: C-K Chris
authors.initials: CK
authors.lastname: Wang
authors.forename: Eric
authors.initials: E
authors.lastname: Maimon
authors.forename: Dianne
authors.initials: D
authors.lastname: Poster
authors.forename: Mohamad
authors.initials: M
authors.lastname: Al-Sheikhly
mesh_terms: D001895:Boron / Q000008:administration & dosage; D016754:Boron Neutron Capture Therapy / Q000379:methods*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D002788:Cholesterol Esters / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006801:Humans; D007554:Isotopes / Q000008:administration & dosage; D018499:Linear Energy Transfer; D008081:Liposomes; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D002788:Cholesterol Esters; D007554:Isotopes; D008081:Liposomes; D001895:Boron
keywords: BNCT; Boron neutron capture therapy; prostate cancer cells; thermal neutron irradiation