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.

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

GIUSTI, VALERIO;
2005-01-01

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.
2005
Kullberg, Eb; Wei, Q; Capala, J; Giusti, Valerio; Malmstrom, P. U. AND GEDDA L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11568/98554
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