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

Int J Radiat Biol. 2014 Jun;90(6):480-5. doi: 10.3109/09553002.2014.901579.

Abstract

Purpose: 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.

Materials and 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.

Conclusion: 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.

Keywords: BNCT; Boron neutron capture therapy; prostate cancer cells; thermal neutron irradiation.

MeSH terms

  • Boron / administration & dosage
  • Boron Neutron Capture Therapy / methods*
  • Cell Line, Tumor
  • Cell Survival / radiation effects
  • Cholesterol Esters / administration & dosage
  • Drug Delivery Systems
  • Humans
  • Isotopes / administration & dosage
  • Linear Energy Transfer
  • Liposomes
  • Male
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*

Substances

  • Cholesterol Esters
  • Isotopes
  • Liposomes
  • Boron