EGF-receptor targeted liposomes with boronated acridine: Growth inhibition of cultured glioma cells after neutron irradiation

Abstract

Purpose: To study survival of cultured U-343MGaCl 2:6 glioma cells after incubation with boron-containing liposomes targeting the epidermal growth factor receptor following neutron irradiation.

Materials and methods: Epidermal growth factor-tagged liposomes were loaded with water-soluble boronated acridine developed for boron neutron capture therapy, (BNCT). Cellular uptake and distribution were studied. Further, cells were placed at 3 cm depth in a phantom and exposed to an epithermal neutron beam to study clonogenic cell survival.

Results: The cellular uptake of boron reached 90 ppm and it was determined by subcellular fractionation that most of the cell-associated boron was located outside of the nucleus. For clonogenic survival, the cells were incubated with epidermal growth factor receptor-targeted liposomes for 4 hours resulting in a cellular concentration of 55 ppm boron (11 ppm ¹⁰B). At a fluence of 3 × 10¹² neutrons/cm² the cell killing effect of the boron-containing epidermal growth factor-liposomes was about ten times higher than for neutrons only. Furthermore, theoretical calculation of the survival by enriched compound (55 ppm ¹⁰B), using the parameters from non-enriched compound (11 ppm ¹⁰B), shows that the killing effect in this case would be approximately five orders of magnitude higher than for neutrons only.

Conclusion: The results in this study show that epidermal growth factor-receptor targeted liposomes are suitable as tumor-cell delivery agents of boron for BNCT and support further studies to demonstrate their effectiveness in vivo.

Keywords:

• Boron neutron capture therapy (BNCT)
• Epidermal growth factor (EGF)
• liposome
• acridine
• clonogenic cell survival